Browsing by Author "Cox, C."

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Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison with culture and Xpert W MTB/RIF
(Researchgate, 2017) Mulder, C.; Mgode, G. F.; Ellis, H.; Valverde, E.; Beyene, N.; Cox, C.; Reid, S. E.; Van’t Hoog, A. H.; Edwards, T. L.
S E T T I N G : Enhanced tuberculosis (TB) case finding using detection rats in Tanzania. O B J E C T I V E S : To assess the diagnostic accuracy of detection rats compared with culture and Xpert w MTB/ RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients. D E S I G N : A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert. R E S U LT S : Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1–79.5) when compared with cul- ture, and up to 81.8% (95%CI 76.0–86.5) when compared with Xpert, which was statistically signifi- cantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9– 45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light- emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone. C O N C L U S I O N : Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear- negative TB patients if more advanced diagnostics are not available
Active tuberculosis detection by pouched rats in 2014: more than 2,000 new patients found in two countries
(2016 Society for the Experimental Analysis of Behavior, 2016) Poling, A.; Beyene, N.; Valverde, E.; Mulder, C.; Cox, C.; Mgode, G.; Edwards, T. L.
Tuberculosis (TB) is a major problem in poor countries because sensitive diagnostic tools are unavail- able. In 2014, our pouched rats evaluated sputum from 21,600 Tanzanians and 9,048 Mozambicans whose sputum had previously been evaluated by microscopy, the standard diagnostic for TB. Evalua- tion by the rats revealed 1,412 new patients with active TB in Tanzania and 645 new patients in Mozambique, increases of 39% and 53%, respectively, when compared to detections by microscopy alone. These results provide further support for the applied use of scent-detecting rats.
From pests to tests: training rats to diagnose tuberculosis
(ERS 2020, 2020) Fiebig, L.; Beyene, N.; Burny, R.; Fast, C. D.; Cox, C.; Mgode, G. F.
2020 is the year of the rat. The rat is the first of the 12 Chinese zodiac signs, and represents spirit, alertness, flexibility and vitality. In respiratory medicine, we may think of rats as vectors for diseases, such as pulmonary forms of hantavirus disease or leptospirosis, and pneumonic plague. Rodent control is thus part of hygiene guidelines and the International Health Regulations. And yet, the rat’s keen sense of smell has led to its incredible career as a living tuberculosis (TB) detector. The TB detection rat journey began with an idea in Tanzania in 2001, roughly 120 years after the TB-causing Mycobacterium tuberculosis was discovered by microscopy and bacterial culture. African giant pouched rats (Cricetomys ansorgei) had already been successfully trained using positive reinforcement to find explosives [1]. So, the question arose if they could do more for humanity by helping to also combat disease. But how would the rats use their noses to find bacteria or otherwise sniff out TB patients? For centuries, olfaction had already informed diagnostics in medical practices, e.g. in detecting metabolic issues such as ketoacidosis or tissue decay such as gangrene [2]. In the Flemish common language, the word tering, which etymologically refers to the smell of tar, is used for TB. The advent of chromatographic techniques allows characterisation of the organic compounds causing odours.
Mycobacterium genotypes in pulmonary tuberculosis infections and their detection by trained African giant pouched rats
(Springer Science+Business, 2015) Mgode, G. F.; Cohen-Bacrie, S.; Bedotto, M.; Weetjens, B. J.; Cox, C.; Jubitana, M.; Kuipers, D.; Machang’u, R. S.; Kazwala, R.; Mfinanga, S.G.; Kaufmann, S. H. E.; Drancourt, M.
Tuberculosis (TB) diagnosis in low-income countries is mainly done by microscopy. Hence, little is known about the diversity of Mycobacterium spp. in TB infections. Different genotypes or lineages of Mycobacte- rium tuberculosis vary in virulence and induce different inflammatory and immune responses. Trained Cricetomys rats show a potential for rapid diagnosis of TB. They detect over 28 % of smear-negative, culture-positive TB. How- ever, it is unknown whether these rats can equally detect sputa from patients infected with different genotypes of M. tuberculosis. A 4-month prospective study on diversity of Mycobacterium spp. was conducted in Dar es Salaam, Tanzania. 252 sputa from 161 subjects were cultured on Lowenstein-Jensen medium and thereafter tested by rats. Mycobacterial isolates were subjected to molecular iden- tification and multispacer sequence typing (MST) to determine species and genotypes. A total of 34 Mycobac- terium spp. isolates consisting of 32 M. tuberculosis, 1 M. avium subsp. hominissuis and 1 M. intracellulare were obtained. MST analyses of 26 M. tuberculosis isolates yielded 10 distinct MST genotypes, including 3 new genotypes with two clusters of related patterns not grouped by geographic areas. Genotype MST-67, shared by one- third of M. tuberculosis isolates, was associated with the Mwananyamala clinic. This study shows that diverse M. tuberculosis genotypes (n = 10) occur in Dar es Salaam and trained rats detect 80 % of the genotypes. Sputa with two M. tuberculosis genotypes (20 %), M. avium homin- issuis and M. intracellulare were not detected. Therefore, rats detect sputa with different M. tuberculosis genotypes and can be used to detect TB in resource-poor countries.
Mycobacterium tuberculosis volatiles for diagnosis of tuberculosis by Cricetomys rats
(Elsevier, 2012-07-12) Mgode, G. F.; Weetjens, B.; Nawrath, T.; Lazar, D.; Cox, C.
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 ¼ 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.
Pouched rats’ detection of tuberculosis in human sputum: Comparison to culturing and polymerase chain reaction
(Tuberculosis Research and Treatment, 2012) Mahoney, A.; Weetjens, B. J.; Cox, C.; Beyene, N.; Reither, K.; Makingi, G.; Jubitana, M.; Kazwala, R. R.; Mfinanga, G. S.; Kahwa, A.; Durgin, A.; Poling, A.
Setting. Tanzania. Objective. To compare microscopy as conducted in direct observation of treatment, short course centers to pouched rats as detectors of Mycobacterium tuberculosis. Design. Ten pouched rats were trained to detect tuberculosis in sputum using operant conditioning techniques. The rats evaluated 910 samples previously evaluated by smear microscopy. All samples were also evaluated through culturing and multiplex polymerase chain reaction was performed on culture growths to classify the bacteria. Results. The patientwise sensitivity of microscopy was 58.0%, and the patient-wise specificity was 97.3%. Used as a group of 10 with a cutoff (defined as the number of rat indications to classify a sample as positive for Mycobacterium tuberculosis) of 1, the rats increased new case detection by 46.8% relative to microscopy alone. The average samplewise sensitivity of the individual rats was 68.4% (range 61.1–73.8%), and the mean specificity was 87.3% (range 84.7–90.3%). Conclusion. These results suggest that pouched rats are a valuable adjunct to, and may be a viable substitute for, sputum smear microscopy as a tuberculosis diagnostic in resource-poor countries.
Serological and molecular characterization of leptospira serovar Kenya from captive African giant pouched rats (Cricetomys gambianus) from Morogoro Tanzania
(2004-03-07) Machangu, R.S.; Mgode, G.F.; Assenga, J.; Mhamphi, G.; Weetjens, B.; Cox, C.; Verhagen, R.; Sondij, S; Goris, M.G.; Hartskeerl, R.A.
Two identical leptospiral isolates coded Sh9 and Sh25 obtained from the urine of captive African giant pouched rats (Cricetomys gambianus), destined for use as biodetector of antipersonnel landmines were typed as serovar Kenya using cross-agglutination absorption test and DNA fingerprinting with the insertion element sequences IS1533 and IS1500 derived primers. The two isolates were previously characterized using cultural and serological – microagglutination test as pathogenic leptospires of the serogroup Ballum, closely related to serovars Kenya and Peru. To our knowledge, this is the first reported in-depth characterization of leptospira isolates from Tanzania.
Tuberculosis detection by pouched rats: Opportunities for reinforcement under low-prevalence conditions
(2017 Elsevier B.V, 2017) Edwards, T. L.; Ellis, H.; Watkins, E. E.; Mulder, C.; Mgode, G.; Cox, C.; Poling, A.
Giant African pouched rats (Cricetomys ansorgei) have been employed successfully in two operational tuberculosis-detection projects in which they sniff sputum samples from symptomatic individuals who have visited tuberculosis clinics. The prevalence of pulmonary tuberculosis in this population is high, approximately 20% in the regions where the rats have been used. If the rats are to be used to screen individuals from lower- prevalence populations, their performance under such conditions must first be evaluated. In this study, the prevalence of tuberculosis-positive samples presented to eight pouched rats was reduced to approximately 5%, and the percentage of known-positive samples included as opportunities for reinforcement was varied in sequence from 10 to 8, 6, 4, 2, 4, and 2. Liquid food reinforcers were delivered for identification responses to known-positive samples and at no other time. The rats’ accuracy was clinically and statistically significantly lower at 2% than at the other values. These results indicate that the rats can perform well in low-prevalence scenarios but, if they are used under the conditions of the present study, at least 4% of the samples presented to them must be opportunities for reinforcement.
Using giant african pouched rats to detect human tuberculosis: A review
(Pan African Medical Journal, 2015-08-31) Poling, A.; Mahoney, A.; Beyene, N.; Mgode, G.; Weetjens, B.; Cox, C.; Durgin, A.
Despite its characteristically low sensitivity, sputum smear microscopy remains the standard for diagnosing tuberculosis (TB) in resource-poor countries. In an attempt to develop an alternative or adjunct to microscopy, researchers have recently examined the ability of pouched rats to detect TB-positive human sputum samples and the microbiological variables that affect their detection. Ten published studies, reviewed herein, suggest that the rats are able to detect the specific odor of Mycobacterium tuberculosis , which causes TB, and can substantially increase new-case detections when used for second-line TB screening following microscopy. Further research is needed to ascertain the rats' ability to detect TB in children and in HIV-positive patients, to detect TB when used for first-line screening, and to be useful in broad-scale applications where cost- effectiveness is a major consideration.