Trained rats could represent the answer to the need for more effective ways of diagnosing tuberculosis (TB) in children, according to researchers at Sokoine University of Agriculture in Tanzania. Studies by Georgies F. Mgode and colleagues demonstrated how specially trained African giant pouched rats were able to sniff out 68% more cases of TB infection in children’s sputum samples than could be diagnosed by standard smear microscopy tests. The rats are trained to detect a specific combination of volatile organic compounds produced by Mycobacterium tuberculosis, the bacterium that causes TB, and can distinguish between M. tuberculosis and other pathogenic organisms both in culture and in sputum samples.

Reporting on their studies in the journal Pediatric Research, Dr. Mgode’s team concludes, “Trained rats increase pediatric TB detection significantly and could help address the pediatric TB diagnosis challenges.” Their published paper is entitled, “Pediatric tuberculosis detection using trained African giant pouched rats.”

Sub-Saharan Africa and South East Asia are among global regions with the highest burden of TB, a disease that killed nearly 1.3 million people worldwide in 2016, including 130,000 children, the researchers note. However, a large proportion of TB patients remain undetected in high-burden areas due to the poor sensitivity of standard smear microscopy techniques that commonly represent the mainstay of diagnosis.

Pediatric TB is particularly difficult to diagnose because of the low levels of bacteria in sputum samples, the authors write. Children under five years of age also tend to produce poor-quality sputum, “compromising the quality of smear-microscopy results in TB clinics.” So while the sensitivity of adult sputum culture is 80%, mycobacteriological confirmation of pediatric TB infection by smear microscopy and culture yields < 15% and between 30% and 40% sensitivities, respectively, they state. “Many children with TB are not bacteriologically confirmed or not even diagnosed, which has major implications for their treatment success rate,” the authors write. “There is a need for new diagnostic tests to enhance TB detection in children, especially in low- and middle-income countries.”

Trained TB detection rats have already been used Tanzania and Mozambique “as an enhanced case-finding tool under research, after smear microscopy, ”and have increased TB case detection by more than 40%, the authors comment. However, these prior reports have focused on adult TB, whereas the latest Sokoine University of Agriculture study was “unique” in its specific focus on diagnosing TB in children.

Sputum samples from 55,148 presumptive TB patients—including 982 children aged 1–5 years—who attended 24 directly observed treatments, short-course (DOTS) clinics in two regions of Tanzania were tested by smear microscopy, and were then sent to the Sokoine University of Agriculture’s non-profit partner organization, APOPO (“Anti-Personnel Landmines Detection Product Development”) for assessment by trained rats. Samples identified as positive for TB by the rats were then confirmatory tested using light-emitting diode fluorescence microscopy (LED-FM). Positive results were sent to the DOTS center and to healthcare workers so the patients could be tracked to start TB treatment.

The results showed that whereas the clinics detected 34 bacteriologically confirmed TB patients aged 1–5 years, the rats detected another 23 TB-positive children, representing a 67.6% increase in detection in this age group. And while the clinics detected TB in 94 children aged 6–10 years, another 35 bacteriologically confirmed cases were identified by the rats, increasing detection in the 6–10 age group by 37.2%.

Cases in older agegroups were also more likely to be identified by the rats than by the clinics, although the differences were not so significant. The rats increased the case detection of adolescents by 22.8%, and of adults by 33.7%. For a typical pediatric group (aged 1–14 years), the rats increased the detection rate by 62.8%. “The increase in pediatric TB case detection rate (67.6%) was statistically significantly higher than the increase found in age groups older than 5 years,” the authors state. “The proportion of smear-positive TB patients missed by DOTS microscopy who were detected by rats was statistically significantly higher in children aged 1–14 years than in adults, indicating that trained rats can help address the difficulties of detecting pediatric TB associated with sputum quality and bacilli load that can be below the detection limits of conventional smear microscopy.”

“Notably, the younger age groups, for which the rats were most effective at identifying TB cases missed by smear microscopy, were also those for which sputum samples contained fewest bacteria,” the team comments. “The observation that rats produced higher additional yield in samples with scanty bacilli than in samples with more bacilli suggests that despite quality and quantity, sputum from children with TB contains an adequate amount of Mycobacterium tuberculosis-specific volatile-odor compounds, enabling rat detection.”

The researchers suggest that the use of detection rats could represent “a major step forward” in TB control. “This intervention involving TB screening by trained rats and community based patient tracking of new TB patients missed by hospitals enables treatment initiation of up to 70%,” Dr. Mgode notes. “This is a significant proportion given that these additional patients were considered TB negative in hospitals, hence were initially left untreated.”

The researchers also advocate investigating whether rats can be trained to detect TB in urine or other samples, such as gastic lavage or nasopharyngeal aspiration. “Further determination of accuracy of rats involving other sample types is still needed…Urine could provide noninvasive sampling, whereas gastric and nasopharyngeal aspiration are widely used when children cannot produce sputum samples.”

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