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Rats sniff out tuberculosis

Lisa Grauer

More than just a pretty face, the African giant pouched rat can detect tuberculosis in sputum samples using its superior sense of smell.

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Researchers in Tanzania have tapped into a novel resource for detecting tuberculosis (TB): giant rats. Using their olfactory acumen, these animals can differentiate between sputum samples from TB-infected and non-infected patients more accurately than current microscopy diagnostic techniques. Although somewhat unorthodox, these rats may eventually provide a fast, simple, and efficient method of first-line screening for TB.

In the December 2010 issue of the American Journal of Tropical Medicine and Hygine, Bart Weetjens, founder and development director of the social enterprise Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling (APOPO) based in Tanzania, Africa, and colleagues reported on a study that found the use of sniffer rats improved TB detection by 44% over the use of microscopy alone. In the study, sniffer rats were presented with previously analyzed TB sputum samples collected from Direct Observation Treatment Short-Course (DOTS) centers in Dar es Salaam, Tanzania.

Bart Weetjens with a sniffer rat. Source: Xavier Rossi photography

Out of 10,523 patient samples, the DOTS centers confirmed 1403 as TB-positive. The sniffer rats detected these 1403 TB-positive patients but also identified an additional 620 TB-positive patients. Samples identified as positive by the rats were all confirmed using microscopy using the Ziehl Neelson (ZN) method—a staining technique for TB testing that takes advantage of the ability of certain bacteria to resist acid de-staining procedures.

“Rat detection of TB is considered a second-line screen where samples that have been previously tested are collected from hospitals and then re-tested by rats,” said Weetjens. “The real power in using rats is that they can process very large volumes of samples in a very short time. A technician can analyze 40 samples in a day, but a rat can do it in 7 minutes.”

Although generally imperceptible to humans, sniffer rats with their keen sense of smell can detect minute quantities of Mycobacterium tuberculosis, the bacteria responsible for TB, which emits a specific volatile compound with a characteristic tar-like odor.

A sniffer rat detecting TB-positive sputum samples.Source: APOPO

Sniffer rats are trained to detect TB based on the principal of associative response conditioning: each rat is taught to associate the popping sound of a metal clicker with a food reward. Once conditioned to associate the clicking sound with a reward, trainers expose the rats to gradually increasing numbers of known TB-positive or negative sputum samples, using the clicker each time the rat sniffs a positive sample. In this way, rats are trained to indicate positive samples by keeping their nose in the “sniffing holes” of a specially designed cage under which the sputum samples are placed.

“Rats have many advantages from a logistics point of view: they’re easy to train, they require a low level of skill, they’re easy to maintain, they don’t require a lot of space or medical care, they’re quite resilient to tropical diseases, they’re a local and renewable resource, and they’re cheaper to train than dogs,” said Weetjens.

But despite the cost and time advantages, the African medical community has been reluctant to adopt rats in TB detection. “There’s no real procedure for accrediting diagnostics like there is for drugs and clinical trials,” says Weetjens.

In 2002, Weetjens was training the rats to sniff out landmines when he heard a World Health Organization announcement about the prevalence of TB in African. “They expected a steep increase in TB cases, going from 2 million to 8 million cases annually,” he said. “Comparatively, there are 6000 to 10,000 landmine casualties annually. That immediately showed me the severity of this epidemic.”

Africa comprises 13 of the 15 countries with the highest TB burden, with the epidemic exacerbated by the high incidence of HIV co-infection. In some sub-Saharan African countries, 80% of TB patients are also infected with HIV, but despite TB killing more HIV-infected people than any other disease, only 1% of these individuals are actually screened for TB.

Weetjens hopes that one day rat detection of TB will be used as a first-line screen. In the interim, he plans to expand the number of TB detection clinics from the current 7 to 26 if funding permits, as well as improve upon detection methods for second-line screening by training rats to detect TB in smear samples rather than sputum.

The paper “Using giant African rats to detect tuberculosis in human sputum samples: 2009 findings” was published in the December 2010 issue of the American Journal of Tropical Medicine and Hygiene.