title: Diagnosis of tuberculosis by trained African giant pouched rats and confounding impact of pathogens and microflora of the respiratory tract.
abstract: Trained African giant-pouched rats (Cricetomys gambianus) can detect Mycobacterium tuberculosis and show potential for the diagnosis of tuberculosis (TB). However, rats' ability to discriminate between clinical sputum containing other Mycobacterium spp. and nonmycobacterial species of the respiratory tract is unknown. It is also unknown whether nonmycobacterial species produce odor similar to M. tuberculosis and thereby cause the detection of smear-negative sputum. Sputum samples from 289 subjects were analyzed by smear microscopy, culture, and rats. Mycobacterium spp. were isolated on Lowenstein-Jensen medium, and nonmycobacterial species were isolated on four different media. The odor from nonmycobacterial species from smear- and M. tuberculosis culture-negative sputa detected by ≥2 rats ("rat positive") was analyzed by gas chromatography-mass spectrometry and compared to the M. tuberculosis odor. Rats detected 45 of 56 confirmed cases of TB, 4 of 5 suspected cases of TB, and 63 of 228 TB-negative subjects (sensitivity, 80.4%; specificity, 72.4%; accuracy, 73.9%; positive predictive value, 41.7%; negative predictive value, 93.8%). A total of 37 (78.7%) of 47 mycobacterial isolates were M. tuberculosis complex, with 75.7% from rat-positive sputa. Ten isolates were nontuberculous mycobacteria, one was M. intracellulare, one was M. avium subsp. hominissuis, and eight were unidentified. Rat-positive sputa with Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus spp., and Enterococcus spp. were associated with TB. Rhodococcus, Nocardia, Streptomyces, Staphylococcus, and Candida spp. from rat-positive sputa did not produce M. tuberculosis-specific volatiles (methyl nicotinate, methyl para-anisate, and ortho-phenylanisole). Prevalence of Mycobacterium-related Nocardia and Rhodococcus in smear-negative sputa did not equal that of smear-negative mycobacteria (44.7%), of which 28.6% were rat positive. These findings and the absence of M. tuberculosis-specific volatiles in nonmycobacterial species indicate that rats can be trained to specifically detect M. tuberculosis.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Campus Charité Mitte, Berlin, Germany.
authors.forename: Georgies F
authors.initials: GF
authors.lastname: Mgode
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Weetjens
authors.forename: Thorben
authors.initials: T
authors.lastname: Nawrath
authors.forename: Christophe
authors.initials: C
authors.lastname: Cox
authors.forename: Maureen
authors.initials: M
authors.lastname: Jubitana
authors.forename: Robert S
authors.initials: RS
authors.lastname: Machang'u
authors.forename: Stéphan
authors.initials: S
authors.lastname: Cohen-Bacrie
authors.forename: Marielle
authors.initials: M
authors.lastname: Bedotto
authors.forename: Michel
authors.initials: M
authors.lastname: Drancourt
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D032761:Animal Experimentation; D000818:Animals; D001419:Bacteria / Q000302:isolation & purification* / Q000472:pathogenicity*; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D051381:Rats; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology*; D014376:Tuberculosis / Q000175:diagnosis*; D055815:Young Adult