Trained Rats Increased Tuberculosis Detection Rates by 44 Percent Over Microscopic Analysis


Trained giant African rats increased positive TB detection rates by 44 percent over microscopy, the most commonly-used technique for diagnosing TB, according to a new study released in the December issue of the American Journal of Tropical Medicine and Hygiene.

The study, utilizing trained giant African pouched rats, analyzed sputum samples of 10,523 patients from five Direct Observation Treatment Short-Course (DOTS) centers in Tanzania. The samples were first analyzed through microscopy by technicians at the DOTS center then provided to Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling (APOPO) in Tanzania for second-line analysis by the rats. While traditional microscopic analysis found 13.3 percent of patients to be TB-positive, second-line screening by the rats revealed 620 new TB-positive patients.

"Using sniffer rats to detect TB seems medieval but our study shows it works, providing an inexpensive, accurate, quick diagnostic," says lead investigator Alan Poling, PhD, of Western Michigan University. "This could have a huge impact in developing countries where TB accounts for one-fourth of all preventable adult deaths and high-tech screening methods arent readily available."

TB is the No. 1 infectious disease killer in the world, responsible for approximately 3 million deaths per year. Serious illness or death from TB can be prevented if detected and treated early enough. But, the most common technique for diagnosing TB, sputum smear microscopy using the Ziehl Neelsen (ZN) method, often leads to inaccurate and missed diagnoses.

"Millions of people die needlessly every year from preventable infectious diseases due to delayed detection and treatment. We must work to find innovative tools that increase our ability to detect, treat and prevent disease." says Peter Hotez, MD, PhD, president of the American Society of Tropical Medicine and Hygiene. "This study provides a realistic, easy-to-implement diagnostic solution for communities that may not have access to other tools. This study leads the way to our goal of reducing the impact of TB on the world, and exploring how this might be used to detect other diseases."

Ten giant African pouched rats (Cricetomys gambianus) were trained to screen sputum samples. They were rewarded with banana for pausing at sputum samples known to contain M. tuberculosis but not for pausing at other sputum samples. Through such training, they learned to pause reliably only at samples that were positive for TB. The status of samples with respect to microscopy was known and the rats were rewarded with food when they kept their nose in a hole above a TB-positive sample for at least 5 seconds, which defines an indicator response.

Twenty-three thousand, one hundred one (23,101) sputum samples from 10,523 patients were screened by DOTS center microscopists, and then by the rats. The DOTS center microscopists found 2,487 positive sputum samples, taken from 1,403 different patients (13.3 percent of all patients tested). The rats as a group identified 2,274 of these samples and 1,335 of these patients as TB-positive. The rats also identified as TB-positive 3,012 DOTS-negative samples and 1,418 DOTS-negative patients. Analysis of smears by APOPOs microscopists confirmed the presence of M. tuberculosis in 927 of these smears, which came from 620 different patients. Thus, the use of rats in simulated second-line screening increased the new-case detection rate by 44 percent. Overall, there were 2,085 rat-positive samples and 898 rat-positive patients in which the TB bacillus was not evident to microscopists at the DOTS centers or at APOPO. Thus, when multiple rats evaluated the same sample, the overall sample-wise and patient-wise specificities were 89 percent and 90 percent, respectively.

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