Global WACh

June 29, 2022

New publication in the Lancet Microbe on CRISPR detection of tuberculosis in adults and children with HIV.

Mycobacterium tuberculosis (TB) remains a major factor in global morbidity and mortality, especially for adults and children with HIV. Coinfection of HIV and tuberculosis is uniquely dangerous, as the depression of normal immune response to infection in persons with HIV can lead to both severe illness and the underdiagnosis of TB when using sputum-based assays. Collecting sputum from young children presents further issues. A new molecular diagnostics study by UW Global WACh in collaboration with Tulane University and other partners including Baylor College of Medicine, Baylor Children’s Foundation-Eswatini, University of Nairobi and Kenyatta National Hospital in Kenya, to study the effectiveness of CRISPR-based assay detection of M. tuberculosis cell-free DNA (Mtb-cfDNA) in seropositive adults and children was published in The Lancet Microbe May 2022 edition. 

Analysis of the CRISPR-TB assay was performed using stored blood samples from adults and children with TB and their asymptomatic household contacts in Eswatini and  children living with HIV (CLHIV) that are at high risk of TB, which were previously enrolled in the completed PUSH trial. CRISPR-TB detected all children with confirmed tuberculosis and additionally identified 80% of children with unconfirmed TB that was undiagnosed with traditional methods such as Xpert and TB culture. CLHIV who were CRISPR-TB positive at enrolment had a 2·4-times higher risk of mortality by 6 months after enrolment. Mtb-cfDNA signal decreased after tuberculosis treatment initiation, with near or complete Mtb-cfDNA clearance by 6 months after tuberculosis treatment initiation indicating its potential for TB treatment response.

Looking forward, the group plans to evaluate this promising platform in a newly developed cohort of children suspected with TB in Nairobi, Kenya, continuing our partnership with the Hu lab at Tulane University and with a new collaboration with Kenya Medical Research Institute (KEMRI) Centre for Respiratory Diseases Research (CRDR) under the leadership of Dr. Videlis Nduba and UW MPH Epidemiology and IARTP program alumnus. Congratulations to the research team on this exciting publication! 

Read the full paper here.