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|Year : 2013 | Volume
| Issue : 2 | Page : 114--116
Rapid diagnosis of infectious diseases: The role of giant African pouched rats, dogs and honeybees
Department of Microbiology, Bhopal Memorial Hospital and Research Centre, Karond, Bhopal, Madhya Pradesh, India
Department of Microbiology, Bhopal Memorial Hospital and Research Centre, Karond, Bhopal, Madhya Pradesh
Early detection of infection in an individual is an important strategy to prevent transmission and spread of the infection - in the community or among patients admitted in a health care facility. Over the past decade, there have been rapid advances in technology in an attempt to provide rapid, accurate tests for diagnosis of infectious diseases. With this in perspective, the use of animals«SQ» superior olfactory sensitivity to sniff out infectious diseases holds promise.
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Desikan P. Rapid diagnosis of infectious diseases: The role of giant African pouched rats, dogs and honeybees.Indian J Med Microbiol 2013;31:114-116
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Desikan P. Rapid diagnosis of infectious diseases: The role of giant African pouched rats, dogs and honeybees. Indian J Med Microbiol [serial online] 2013 [cited 2019 Oct 17 ];31:114-116
Available from: http://www.ijmm.org/text.asp?2013/31/2/114/115214
Early detection of infection in an individual is an important strategy to prevent transmission and spread of the infection - in the community or among patients admitted in a health-care facility. Over the past decade, there have been rapid advances in technology in an attempt to provide rapid, accurate tests for diagnosis of infectious diseases. As welcome as these advances have been, their utility needs to be put into perspective, particularly in a developing country like ours.
The utility of any diagnostic test is a function of the test characteristics of the diagnostic technology (that is, the sensitivity and specificity of the test), access to the results, which depends on the level of infrastructure required to use the diagnostic test and the time required to obtain results. An important factor remains the availability of laboratory infrastructure required to perform them. In our country, we have three categories of health-care facilities: Facilities with advanced infrastructure (as found in referral centres and corporate hospitals); reasonably well-equipped facilities with moderately updated infrastructure (as found in many urban health-care facilities); and facilities with minimal or no infrastructure (as found in most of the peripheral health centres located in rural/tribal areas). A very small proportion of our population has access to facilities with advanced infrastructure and the largest proportion of our population has access only to facilities with minimal or no infrastructure. Quite obviously, the utility of any new rapid diagnostic test will increase in proportion to the capacity of the population to access the test. 
With this in perspective, the use of animals' superior olfactory sensitivity to sniff out infectious diseases holds promise. Since micro-organisms produce volatile organic compounds, it would be possible to smell them. A recent proof of principle study investigated whether a dog's superior olfactory sensitivity could be used to detect Clostridium difficile in stool samples and patients admitted in hospital.  The study was conducted in two large Dutch teaching hospitals. A 2 year old beagle was trained to identify the smell of C. difficile (by sitting or lying down when C. difficile could be smelt) and tested on 300 patients (30 diagnosed with C. difficile infection and 270 controls). The dog's sensitivity and specificity for identifying C. difficile in stool samples were 100% (95% confidence interval 91-100%). During the detection rounds in the hospital, the dog correctly identified 25 of the 30 cases and 265 of 270 controls.
A similar exercise had been carried out earlier by training giant African pouched rats to detect the presence of Mycobacterium tuberculosis in sputum samples. ,,, Like dogs, giant African pouched rats (Cricetomys gambianus) are used operationally to detect land mines. These large rats, native to much of Africa, have an excellent sense of smell and detect tuberculosis (TB) by sniffing sputum samples. They are trained to respond consistently in one-way (they pause) if the sample contains M. tuberculosis and respond in another way (they do not pause) if the sample does not contain the bacillus. Each rat can test hundreds of samples each day; thus, facilitating high volumes of inexpensive testing with minimal infrastructure.
In order to determine the rats' ability to discriminate between sputa containing other Mycobacterium spp. and non-mycobacterial organisms, sputum samples from 289 subjects were analysed by smear microscopy, culture and rats.  Mycobacterium spp. were isolated on Lowenstein-Jensen medium and non-mycobacterial species were isolated on four different media. The odour from non-mycobacterial species from smear- and M. tuberculosis culture-negative sputa detected by ≥2 rats ("rat positive") was analysed by gas chromatography-mass spectrometry and compared to the M. tuberculosis odour. 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 non-tuberculous 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). These findings and the absence of M. tuberculosis-specific volatiles in non-mycobacterial species indicate that rats can be trained to specifically detect M. tuberculosis.
Going further, even honeybees (Apis mellifera) were evaluated for their capacity to detect the presence of M. tuberculosis.  The proboscis extension reflex in honeybees was evaluated for detection of tuberculosis. Restrained bees were tested with methyl phenylacetate, methyl p-anisate and methyl nicotinate, previously identified from M. tuberculosis cultures, to determine honeybee capacity for signature volatile compound detection. Methyl p-anisate and methyl phenylacetate were detectable over eight orders of magnitude and honeybees showed proboscis extension response down to 0.1 pg loading of methyl p-anisate on filter paper. It was concluded that potential exists for trained honeybees in non-invasive diagnostic tests for TB.
What does all this augur for rapid diagnostics for infectious diseases as a whole? Given the fact that access to the diagnostic is a crucial function of its utility, how accessible would these tests be? The inputs required would be animal housing facilities and professional trainers. If peripheral centres are unable to provide these inputs, would it be possible to have a centralized facility with the animals being transported to peripheral centres on a fixed schedule? What would the costs be like? These are issues that could be worked out.
The other issues; however, would be a little more difficult to work out. These issues would include acceptance of a diagnosis made on the basis of "dog positive" or "rat positive" or "honeybee positive" tests. How would the very real possibilities of an asymptomatic upper respiratory tract infection or a local allergic reaction of the nasal mucosa in the dog or rat impact the results of the test? Would strong, unrelated smells in the environment affect their ability to sniff out the pathogen? Would any perceived threat in the environment agitate the animals and interfere with their capacity to focus on the smells? These and other issues that might arise with the use of animals in a developing country like ours would need to be examined in larger trials in the field.
The power of the canine nose has an increasingly valuable place in human medicine. Dogs have been trained to detect cancers of the bladder, lung, prostate, ovary, breast and skin. These cancers, in many cases, are often detected before the patient knows of the disease. It, therefore, seems to be a logical extension to use these canine abilities to detect infectious diseases as well. Many advances in medical science have been the result of thinking out of the box. Use of animal faculties for rapid diagnosis of infectious diseases may wellturnout to be one such instance.
Having said that, I must admit to having wondered what the status of microbiologists would be if animals are trained to identify micro-organisms. Much effort and time is spent in training microbiologists and our experience is garnered over years of painstaking work. Would all this just go to the dogs, in more ways than one?
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