Using Giant African Pouched Rats to Detect Tuberculosis in Human Sputum Samples: 2009 Findings

Abstract

Tuberculosis is a major public health problem in developing countries, 1 where sputum smear microscopy is the most common technique for diagnosing the disease. This method has limitations, the most serious being inaccuracy, when large numbers of sputum samples are analyzed.2 Hence, alternative diagnostic tools are badly needed. In recent years, researchers have explored the possibility of using trained giant African pouched rats ( Cricetomys gambianus ), to screen sputum samples rapidly and accurately. A recent study 3 reported that 18 of 20 pouched rats could detect the presence of Mycobacterium tuberculosis in sputum samples at least as well as, and more quickly than, trained microscopists using the standard Ziehl Neelsen (ZN) method. 3In 2009, the rats analyzed sputum samples collected from five Direct Observation Treatment Short-Course (DOTS) centers in Dar es Salaam, Tanzania.4 Sputum samples were used to prepare microscope slides that were stained by the ZN method and evaluated under light microscopes by technicians at the DOTS centers. Sputum remaining after smears were prepared was frozen and the samples were sent to Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling (APOPO) for subsequent analysis by the rats. Thus, the rats were used in a context that approximated second-line tuberculosis (TB) screening. This work describes their performance in that capacity.Ethical clearance to conduct the reported research was obtained from the Tanzanian National Institute for Medical Research. The manner in which rats were maintained, trained, and used in evaluating sputum samples is detailed elsewhere. 3,5 In brief, they were rewarded with a mouthful of 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. In simulated second-line screening the rats worked in a 10-hole stainless steel cage 205 cm long, 55 cm wide, and 55 cm high, shown elsewhere.3 Sputum samples obtained from the DOTS centers and autoclaved to kill infectious microorganisms were presented in small pots located immediately below the holes. 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. Indicator responses to samples deemed by microscopists to be TB-negative were of particular interest, because such responses may indicate detection of TB-positive cases initially missed by the DOTS centers.Ten rats evaluated every sample. Any sample reported as TB-negative by a DOTS center but TB-positive by two or more rats was evaluated by a second ZN microscopic analysis performed by a technician in our laboratory. Those cases found positive in this analysis were designated as new case detections. They were reported to the appropriate DOTS Centers for follow-up testing and, if appropriate, treatment.In 2009, 23,101 sputum samples from 10,...

Pediatric tuberculosis detection using trained African giant pouched rats

“…Nevertheless, still more than a quarter of the adults with smear-positive TB were missed by the DOTS clinics. Previous studies have shown that the TB case detection rate increases by over 40% in the general population when trained rats are used as an enhanced case-finding tool (6,7). In the present study, rats increased case detection by 33.7% in adults that is slightly lower than 40% reported previously.…”

“…Trained TB detection rats have been in use in Tanzania and Mozambique as an enhanced case-finding tool under research, after smear microscopy, whereby they have increased TB case detection by over 40% (6,7). In recent years the percent increase in TB detection due to the trained rats has slightly dropped from 40 to 35-37% annually, probably reflecting the improved quality of smear microscopy in the collaborating DOTS centers.…”

Cost-effectiveness in the diagnosis of tuberculosis: choices in developing countries

“…The rats also identified as positive an additional 927 TB samples initially indicated as negative but found in second microscopy to contain the bacillus. The authors concluded that the use of pouched rats for TB detection in developing countries certainly warrants further research [54]. Mgode et al evaluated rats' ability to discriminate between clinical sputum containing other Mycobacteria spp.…”

Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines

“…Giant African pouched rats (Cricetomys gambianus) have been trained to recognize the smell of Mtb-infected sputum [36]. When samples were exposed to ten different rats, 91% of Mtb smear-positive samples were detected [37]. Attempts to mimic the rats using electronic and chromatographic methods have so far been disappointing.…”