PROJECT SUMMARY
Low-resource settings have a high burden of Neisseria gonorrhoeae infection, but insufficient laboratory
infrastructure for diagnostic tests and antimicrobial susceptibility determination, leading to syndromic
management, which misses a high proportion of cases and results in the overuse of antibiotics. Together, those
factors contribute to driving the emergence of antimicrobial resistance (AMR), a global public health threat.
Two novel strategies can combine to address those challenges. First, the use of CRISPR-based technology
permits the development of low-cost, point-of-care (POC) assays, which can be used in resource-limited
settings. Second, determination of molecular resistance markers can facilitate resistance-guided therapy,
thereby reducing the selective pressure towards AMR. The study aims are: 1) adapt and validate existing
CRISPR-based assays for POC detection of N. gonorrhoeae and ciprofloxacin susceptibility, 2) develop a
multiplexed CRISPR-based assay for N. gonorrhoeae cefixime susceptibility, and 3) evaluate the feasibility and
acceptability of the POC N. gonorrhoeae and AMR assays among two health centers in Botswana. The study
is based upon our preliminary work in the development of Cas13a-based diagnostics for N. gonorrhoeae and
ciprofloxacin susceptibility, and will leverage clinical specimens collected as a part of an ongoing trial at the
Massachusetts General Hospital Sexual Health Clinic, as well as through existing collaborations in Botswana.
This Mentored Patient-Oriented Research Career Development Award (K23) supports the career development
of Dr. Lao-Tzu Allan-Blitz, an instructor of medicine with experience in the epidemiology of and novel diagnostic
assays targeting AMR sexually transmitted infections (STI). The K23 will support Dr. Allan-Blitz to develop
expertise in 1) assay development for POC detection, and 2) assay implementation and evaluation. To achieve
the proposed research and training aims, Dr. Allan-Blitz has assembled a team of mentors who are world
experts. Dr. Jacob Lemieux, who is an expert in metagenomics, DNA sequencing, and CRISPR-based assay
development, will serve as the primary mentor. In addition, his Co-Mentorship team includes Dr. Pardis Sabeti,
a world expert in computational genetics, microbial genomics, diagnostic technologies, and disease
surveillance in Africa, and Dr. Shahin Lockman, a world leader in implementation science research with
longstanding collaborations in Botswana. The proposed research and training aims will leverage strong,
longstanding collaborations and the robust research infrastructure between Brigham and Women's Hospital,
Massachusetts General Hospital, the Broad Institute, and the Botswana Harvard AIDS Institute Partnership.
Finally, the K23 award will advance Dr. Allan-Blitz's career goal of becoming an expert in assay development
for AMR STI and assay implementation, as well as facilitate his transition to research independence.
