For our final post of Diagnostics Weekend, we want to introduce you to an incredible organisation taking diagnostics in a really cool direction. APOPO. APOPO, which celebrates its 20th anniversary this week, saves lives by training African giant pouched rats to detect landmines and tuberculosis. Bart Weetjens created the organisation while looking for a solution for the harm caused by minefields left behind by wars and, having had pet rats as a kid, decided to train rats to detect and help clear landmines. Because the rats were light but intelligent and have a great sense of smell, they could effectively locate the landmines without triggering them and alert their handlers, so humans didn't have to die walking on the minefields -- and not a single rat has, either. If you're concerned about animal welfare, read about how APOPO treats their rats here.
In 2002, APOPO created a new branch of operations: detecting tuberculosis. They could use similar training methods, but now train the highly sensitive rats to detect TB in sputum samples ("A HeroRAT can check 100 sputum samples for tuberculosis [...] just 20 minutes, a job that would take a lab technician using conventional microscopy up to 4 days"). The rats proved to be both accurate and many times faster than previous detection methods. APOPO have operated in Tanzania, Mozambique, Angola, Cambodia, Thailand, Laos, Vietnam, Zimbabwe and Colombia, and has saved many lives by compensating for poor detection equipment in many parts of these countries.
I talked to Lily Shallom from APOPO to learn some more about them.
What inspired the expansion of APOPO's HeroRATs work to TB detection?
APOPO has its headquarters in Tanzania which is one of the 30 high TB burden countries in the world. Being based in Tanzania we encountered the TB problem first hand and seeing how quickly the disease spreads and how often patients are missed and sent home to infect others plus the fact that there is no rapid diagnostic test - we felt a deep need to do something about it.
What are the rats’ strengths and weaknesses for disease detection? Would it be possible to expand their use to other diseases and if so what kind of diseases would they be good for?
I would say their main strength lies in the fact that they are able to detect pretty much anything that has a smell. We are currently investigating to what extent our rats can be trained to detect TB in other ways (e.g. urine or saliva) as well as detection of other harmful diseases, infections, or pathogens from non-invasive biosamples. I feel confident the rats would be very useful in early stage Cancer detection or neurological disease detection. In fact we have found that sometimes the rats indicate consistently on certain samples that all other methods of detection (microscopy, GeneXpert etc) did not find TB. But when there was a follow up a few months later with those patients some of them had developed TB. This is now being investigated further
Weakness might lie in the logistical challenges of using the rats. The samples need to come to our lab and the rats sniff them in a lab setting not out in the public clinics. And for this there needs to be a high throughput of samples. Also the other thing is that they can have a hard time detecting some biological smells that occur in a cocktail - for example in the sputum samples we test there can be other mycobacterium not just mycobacterium tuberculosis and then it gets very complicated for them to smell.
Were there any challenges or unexpected roadblocks when developing the process of training the HeroRATS to detect TB?
The process of training the rats was very straightforward as it was already being done for detecting landmines. We use one of the simplest types of animal learning - called classical conditioning which is based on a stimulus (target smell) producing a response from the rat that tells us they have found that smell. Both TB and landmine detection rats are trained through this operant conditioning, using a combination of a click sound and food rewarding. The challenges were likely to have been in getting enough sputum samples for rats to be trained on and also getting quality samples (getting a sputum sample is quite difficult and you can find some samples are very small or contain a lot of saliva and not enough sputum).
How has the idea of using rats for healthcare been received in clinics, and how did APOPO approach introducing the idea?
Initially most of our partner clinics were sceptical. Rats also have a stigma associated with them so that doesn't help. In particular if the clinics have not heard about us before they find it quite difficult to accept.
We approach this by explaining the challenges of TB diagnosis. In many developing countries, the conventional method of diagnosing tuberculosis is smear microscopy that is only 20-60% accurate depending on the resources available and the skills of technicians. This method may be precise when operated under the right conditions (when a sample is diagnosed as “TB positive” by microscopy, it is almost always a true positive). But many true positives can be missed if conditions are not met and TB is a notoriously difficult disease to detect. We explain how the method that they are using has limitations in sensitivity. For example the distribution of mycobacterium is not even, it is possible that a smear can be made from a portion of sputum that doesn't contain TB mycobacterium. We then explain how good the rats are and show them the outcome of additional cases we have found and usually this is enough to convince them to try. Due to their unique speed and sensitivity, when combined with conventional tuberculosis diagnostics APOPO's HeroRATs have proven to increase detection rates of public clinics by over 40%.
HeroRATs seem like an example of really out-of-the-box thinking, of finding an untapped resource. Are there any other resources, animal or otherwise, you/APOPO think we could be doing more with for public health?
Scent detection is all about the natural super olfactory abilities of animals. We chose rats for a few reasons such as they are too light to set off landmines, they are easy to transport, and the African giant pouched rat is very resistant to disease and heat. So the type of animal is usually chosen because it has attributes useful for its particular job. Thus a guide dog for the blind would be more suitable than a rat. There is much research going on into other diseases and applications that other animals are suitable for, and APOPO is utilising what it knows best.
APOPO's R&D department is currently investigating what increases training success, what exactly the rats are smelling in the sputum samples, alternative ways for the rats to signal that they've found something and indicate their level of certainty, and different types of samples the rats could detect TB from, among other things. You can adopt a HeroRAT or donate to APOPO at apopo.org.