Histopathology-based Surveillance for Mucormycosis

Project Name: Histopathology-based Surveillance for Mucormycosis

Project Status: Proposed

Point of Contact: Rachel Smith

Center: National Center for Emerging and Zoonotic Infectious Diseases

Keywords: Mold surveillance, Histopathology, Mucormycosis

Project Description: Traditionally, the majority of infectious disease surveillance systems have relied on culture-based methods to confirm the presence of infection. However, there are several disease-causing organisms where this is not ideal due to difficulty in culturing the organism. One such example is mucormycetes, formerly zygomycetes, a group of mold species that cause severe, aggressive infection in humans and are inherently resistant to multiple antifungal medications. The last true population-based surveillance for mucormycetes occurred in the San Francisco Bay Area over twenty years ago, and used only culture to measure the incidence of this disease. As these organisms are difficult to culture and definitively diagnosed via histopathology with confirmation by immunohistochemistry and molecular methods at reference laboratories, prior surveillance likely substantially underestimated the burden of disease of these organisms. Understanding the true disease burden is vitally important as the populations at risk for these severe fungal infections, largely immunosuppressed individuals, is increasing due to medical advances. Several recent investigations, including some high-profile outbreaks, continue to remind us of the importance of understanding mucormycete infections.

We propose a pilot surveillance project that seeks to utilize histopathologic surveillance for mucormycosis to better assess the disease burden of this disease. Our proposal aims to build a consortium of 15-20 histopathology labs in the United States that would be a resource for surveillance of infections that require histopathologic diagnosis. This pilot proposal would utilize a novel method of telepathology whereby images of tissue slides in question could be shared electronically with experts in the CDC for real-time consultations, followed by sharing of tissue block with CDC histopathology and fungal experts for case confirmation and organism identification. These real time consultations would serve several purposes. First, they would allow for agreement on suspect cases and which tissue blocks are suitable for diagnosis prior to submission. Second, they would provide submitting institutions with real-time consultation which have the potential to change clinical management. Third, they would show proof of concept for the potential development of a larger telepathology portal at CDC for diagnosis of fungal infections which could be developed in the future, similar to the DPDx site available for parasitic diseases at CDC.

Simultaneously, mucormycete isolates would be collected from the same institutions as the histopathology blocks, if feasible, as well as from an existing consortium of clinical microbiology laboratories (ClinMicroNet) to estimate disease burden through traditional culture methodology. Funds from this pilot would be used to support shipping of isolates as well as salary support for personnel in the MDB laboratory to assist with the additional sequencing work from the influx of isolates.

This pilot will be the first attempt to quantify the burden of mucormycosis using histopathology, not solely culture. Thus, it will provide a more robust estimate of disease burden, and species distribution than prior estimates. Additionally, this consortium of clinical histopathology laboratories could serve other important public health functions. Several other diseases, including mycobacterial and yeast infections would benefit from incorporation of histopathology in surveillance estimates.

We anticipate this pilot to be successful. The Mycotic Disease Branch (MDB) has partnered with the Infectious Diseases Pathology Branch to build the consortium of histopathology labs for this proposal as well as analyze the tissue specimens and data. MDB has worked with ClinMicroNet on a similar call for isolates and in a variety of outbreak settings. Stakeholders in this project include state and local health departments and labs, ClinMicroNet and the academic microbiology and histopathology laboratories participating in this pilot as well as pharmaceutical companies and healthcare providers.

For more information about this project, please contact the CHIIC at chiic@cdc.gov or Brian Lee at brian.lee@cdc.hhs.gov.