Project Details

Early Career

Status: Funded - Open

Stool MTB polymerase chain reaction to improve pediatric TB diagnosis

Alexander Kay, MD


BACKGROUND: 1) Only 10-20% of children with TB are microbiologically confirmed due to poor performance of existing tests. 2) Pediatric diagnostic specimens, obtained through gastric aspirate, sputum induction or nasopharyngeal aspirate, are often not collected because they are invasive, require additional equipment and perform poorly.

GAP: There is a research and data gap on child TB diagnostics using non-respiratory samples, such as stool, to increase test uptake while also maintaining and building on the performance characteristics of traditional samples.

HYPOTHESIS: Hypothesis 1: Compared to the reference standard of culture, stool qPCR will have non-inferior sensitivity and specificity vs. Xpert (comparator test) completed on respiratory specimens.

Hypothesis 2: Stool Xpert performance will be enhanced by stool homogenization and centrifugation, and the MTBDRplus will identify Mtb and molecular drug resistance in DNA isolated via MPFast soil DNA kits.

METHODS: This will be a prospective, cross-sectional, case control study, stool diagnostics will be assessed compared to the traditional diagnostic pathway. Children (age 6 months- 18 years) who are being evaluated for TB will have stool collected in addition to standard diagnostic tests.

RESULTS: Pending

IMPACT: A test that performs similarly to current diagnostics but is used more frequently because it is non-invasive and requires no training for sample collection could increase the microbiologic diagnosis of pediatric TB.

Website Link:


Brunetti, Marie, Sathyanath Rajasekharan, Piluca Ustero, Katherine Ngo, Welile Sikhondze, Buli Mzileni, Anna Mandalakas, and Alexander W. Kay. "Leveraging tuberculosis case relative locations to enhance case detection and linkage to care in Swaziland." Global health research and policy 3, no. 1 (2018): 3.

DiNardo, Andrew R., Alexander W. Kay, Gugu Maphalala, Nadine M. Harris, Celia Fung, Godwin Mtetwa, Pilar Ustero et al. "Diagnostic and Treatment Monitoring Potential of A Stool-Based Quantitative Polymerase Chain Reaction Assay for Pulmonary Tuberculosis." The American journal of tropical medicine and hygiene (2018).

Kay, Alexander W., Shamim M. Islam, Kristen Wendorf, Janice Westenhouse, and Pennan M. Barry. "Interferon-γ Release Assay Performance for Tuberculosis in Childhood." Pediatrics 141, no. 6 (2018): e20173918.

DiNardo, Andrew R., Tomoki Nishiguchi, Emily M. Mace, Kimal Rajapakshe, Godwin Mtetwa, Alexander Kay, Gugu Maphalala et al. "Schistosomiasis Induces Persistent DNA Methylation and Tuberculosis-Specific Immune Changes." The Journal of Immunology (2018): ji1800101.

Sekadde, Moorine Penninah, and Alexander W. Kay. "Tuberculosis Prevention: an Under Prioritized yet Critical Intervention to Reduce Child Tuberculosis Morbidity and Mortality." Current Tropical Medicine Reports 5, no. 1 (2018): 51-58.