Using giant African pouched rats to detect tuberculosis in human sputum samples: 2010 findings

Giant African pouched rats previously have detected tuberculosis (TB) in human sputum samples in which the presence of TB was not initially detected by smear microscopy. Operant conditioning principles were used to train these rats to indicate TB-positive samples. In 2010, rats trained in this way evaluated 26,665 sputum samples from 12,329 patients. Microscopy performed at DOTS centers found 1,671 (13.6%) of these patients to be TB-positive. Detection rats identified 716 additional TB-positive patients, a 42.8% increase in new-case detection. These previously unreported data, which extend to over 20,000 the number of patients evaluated by pouched rats in simulated second-line screening, suggest that the rats can be highly valuable in that capacity

Mycobacterium tuberculosis volatiles for diagnosis of tuberculosis by Cricetomys rats.

Tuberculosis (TB) diagnosis in regions with limited resources depends on microscopy with insufficient sensitivity. Rapid diagnostic tests of low cost but high sensitivity and specificity are needed for better point-of-care management of TB. Trained African giant pouched rats (Cricetomys sp.) can diagnose pulmonary TB in sputum but the relevant Mycobacterium tuberculosis (Mtb)-specific volatile compounds remain unknown. We investigated the odour volatiles of Mtb detected by rats in reference Mtb, nontuberculous mycobacteria, Nocardia sp., Streptomyces sp., Rhodococcus sp., and other respiratory tract microorganisms spiked into Mtb-negative sputum. Thirteen compounds were specific to Mtb and 13 were shared with other microorganisms. Rats discriminated a blend of Mtb-specific volatiles from individual, and blends of shared, compounds (P = 0.001). The rats' sensitivity for typical TB-positive sputa was 99.15% with 92.23% specificity and 93.14% accuracy. These findings underline the potential of trained Cricetomys rats for rapid TB diagnosis in resource-limited settings, particularly in Africa where Cricetomys rats occur widely and the burden of TB is high

Evaluation of giant african pouched rats for detection of pulmonary tuberculosis in patients from a high-endemic setting

This study established evidence about the diagnostic performance of trained giant African pouched rats for detecting Mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (TB) in a high-burden setting.; The TB detection rats were evaluated using sputum samples of patients with presumptive TB enrolled in two prospective cohort studies in Bagamoyo, Tanzania. The patients were characterised by sputum smear microscopy and culture, including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis, and by clinical data at enrolment and for at least 5-months of follow-up to determine the reference standard. Seven trained giant African pouched rats were used for the detection of TB in the sputum samples after shipment to the APOPO project in Morogoro, Tanzania.; Of 469 eligible patients, 109 (23.2%) were culture-positive for Mycobacterium tuberculosis and 128 (27.3%) were non-TB controls with sustained recovery after 5 months without anti-TB treatment. The HIV prevalence was 46%. The area under the receiver operating characteristic curve of the seven rats for the detection of culture-positive pulmonary tuberculosis was 0.72 (95% CI 0.66-0.78). An optimal threshold could be defined at ≥2 indications by rats in either sample with a corresponding sensitivity of 56.9% (95% CI 47.0-66.3), specificity of 80.5% (95% CI 72.5-86.9), positive and negative predictive value of 71.3% (95% CI 60.6-80.5) and 68.7% (95% CI 60.6-76.0), and an accuracy for TB diagnosis of 69.6%. The diagnostic performance was negatively influenced by low burden of bacilli, and independent of the HIV status.; Giant African pouched rats have potential for detection of tuberculosis in sputum samples. However, the diagnostic performance characteristics of TB detection rats do not currently meet the requirements for high-priority, rapid sputum-based TB diagnostics as defined by the World Health Organization

Short report: using giant African pouched rats to detect tuberculosis in human sputum samples: 2009 finding

American journal of tropical medicine and hygiene, 83 (6)), 2010: 1308-1310In 2009, giant African pouched rats trained to detect tuberculosis (TB) evaluated sputum samples from 10,523 patients whose sputum had previously been evaluated by smear microscopy. Microscopists found 13.3% of the patients to be TB-positive. Simulated second-line screening by the rats revealed 620 new TB-positive patients, increasing the case detection rate by 44%. These data suggest that the rats may be useful for TB detection in developing countries, although further research is needed

Short report: using giant African pouched rats to detect tuberculosis in human sputum samples: 2009 finding

American journal of tropical medicine and hygiene, 83 (6)), 2010: 1308-1310In 2009, giant African pouched rats trained to detect tuberculosis (TB) evaluated sputum samples from 10,523 patients whose sputum had previously been evaluated by smear microscopy. Microscopists found 13.3% of the patients to be TB-positive. Simulated second-line screening by the rats revealed 620 new TB-positive patients, increasing the case detection rate by 44%. These data suggest that the rats may be useful for TB detection in developing countries, although further research is needed

Ability of **Cricetomys** rats to detect **Mycobacterium tuberculosis** and discriminate it from other microorganisms

SummaryTrained African giant pouched rats (Cricetomys gambianus) have potential for diagnosis of tuberculosis (TB). These rats target volatile compounds of Mycobacterium tuberculosis (Mtb) that cause TB. Mtb and nontuberculous mycobacteria (NTM) species are related to Nocardia and Rhodococcus spp., which are also acid-fast bacilli and can be misdiagnosed as Mtb in smear microscopy. Diagnostic performance of C. gambianus on in vitro-cultured mycobacterial and related pulmonary microbes is unknown. This study reports on the response of TB detection rats to cultures of reference Mtb, clinical Mtb, NTM, Nocardia; Rhodococcus; Streptomyces; Bacillus; and yeasts. Trained rats significantly discriminated Mtb from other microbes (p < 0.008, Fisher’s exact test). Detection of Mtb cultures was age-related, with exponential and early stationary phase detected more frequently than early log phase and late stationary phase (p < 0.001, Fisher’s test) (sensitivity = 83.33%, specificity = 94.4%, accuracy = 94%). The detection of naturally TB-infected sputum exceeded that of negative sputum mixed with Mtb, indicating that C. gambianus are conditioned to detect odours of TB-positive sputum better than spiked sputum. Although further studies on volatiles from detectable growth phases of Mtb are vital for identification of Mtb-specific volatiles detected by rats, our study underline the potential of C. gambianus for TB diagnosis