Tuberculosis (TB) remains one of the deadliest diseases worldwide, causing over 10 million new infections each year globally. It is estimated that around 28% of the world’s new TB cases occur in India. An estimated 5 lakh deaths occur due to TB each year in the country, which is about one TB death every minute. Despite significant medical advancements, detecting TB remains a major challenge, particularly in remote and underserved populations.
The government’s National TB Elimination Programme (NTEP) aimed to eradicate TB in India by 2025, five years ahead of the global target of 2030, but the chances of this are looking bleak. Despite the India TB Report 2024 revealing a 16% decrease in the incidence of TB (new cases occurring annually) and an 18% decrease in TB-related death since 2015, elimination remains a challenge.
Traditional diagnostic techniques frequently fail to detect TB in its early stages, particularly in children and people with low bacillary loads (M. tuberculosis concentration present in a sputum sample). This means that many cases may go undetected, contributing to the disease’s spread. Many people are also unwilling to seek a second diagnosis if the first test result was negative, and often, are only diagnosed at late stages. Slow and insufficient diagnostic facilities are another issue: residents of rural and remote areas have to travel long distances to get tested. While the government has made TB treatment free, travel is often a big cost for patients. This is where perhaps, innovative approaches could make a significant difference.
African giant pouched rats in TB diagnosis
One such initiative is of APOPO, a non-profit organisation, headquartered in Tanzania and working in 11 countries, that trains African giant pouched rats (nicknamed HeroRATS), to detect TB in sputum samples. “These rats have an outstanding ability to sniff diseases due to their sensitive olfactory receptors,” says Tefera Agizew, head of tuberculosis at APOPO. The rats, he says, demonstrate remarkable accuracy, particularly in detecting cases that traditional methods often miss, serving as a secondary diagnostic tool. Their ability to identify TB quickly and accurately helps improve early diagnosis and curtail transmission particularly in areas with limited healthcare resources. The rats, says Dr. Agizew have successfully transformed TB diagnosis in three countries: Tanzania, Mozambique and Ethiopia.
The rats, bred and nurtured in a facility, undergo a rigorous training process, beginning at just two to three months old, lasting up to nine months | Photo Credit: APOPO HeroRATS via Instagram
The rats, bred and nurtured in a facility, undergo a rigorous training process, beginning at just two to three months old, lasting up to nine months. They are exposed to sputum samples, and when they successfully identify TB-positive samples, researchers signal their success with a clicking sound, followed by a reward of a smoothie made from avocado, ground chow pellets, and banana. This positive reinforcement helps hone their skills. Remarkably, 100 samples can be tested in just 20 minutes, a process typically taking a technician three to four days using conventional sputum-smear microscopy.
The rat’s food habits are otherwise controlled. They are fed during and after testing. Each morning, APOPO staff collect test samples from Directly Observed Therapy (DOT) facilities for reassessment. Samples are placed under ten sniffing holes in a rectangular chamber (205 cm x 55 cm x 55 cm) and evaluated by an average of five rats daily. Trained through operant conditioning, the rats signal a positive response by holding their nose in a scent hole for three seconds or longer. Handlers monitor and record these responses, and rat-positive samples are further analyzed using Ziehl-Neelsen (ZN) microscopy and fluorescent microscopy.
Trained through operant conditioning, the rats signal a positive response by holding their nose in a scent hole for three seconds or longer | Photo Credit: APOPO HeroRATS via Instagram
A study published in BMC Infectious Diseases last April, demonstrated that these rats were able to detect increased tuberculosis cases in both children and adults in Tanzania. TB is generally difficult to detect in children, but the rats identified it at twice the rate compared to conventional testing, the study said. The study looked at 35,766 patients, of whom 5.3% (1900/35,766) were smear-positive and 94.7% (33,866/35,766) were smear or Xpert-negatives. Of those with negative results, 2,029 TB cases were detected using rats, which otherwise would have been missed, the paper said. “They could detect six times more when the bacillary load is scanty or 1+ compared to 2+ or 3+ in both children and adults,” says Dr. Agizew, who was also the lead researcher of the study. Other studies on rats detecting drug-resistant TB are ongoing.
Disease detection by animals
African giant pouched rats aren’t the only animals capable of detecting diseases and TB is not the only disease where animals have been used. Some animals excel where technology falls short. Dogs for instance, are widely used: they have between 125 million and 300 million olfactory receptors and a special sensory organ called the Jacobson’s organ located in their nasal passage, specifically designed to detect pheromones and other chemical signals. Some research indicates that trained dogs may be able to identify Parkinson’s disease.
Unlike dogs, who require extensive training, ants learn quickly and inexpensively, making them a promising alternative for cancer detection. “Insects can help us develop diagnostic tools faster,” says Debajit Saha, assistant professor at Michigan State University, U.S. A French study, published in Science Direct, found that ants detected cancer cells in three days using chemical cues and a sugar reward. Their ability to distinguish cancer types highlights their medical potential. “Our findings suggest ants can serve as fast, feasible, and less laborious living tools for detecting cancer biomarkers,” says lead researcher Baptiste Piqueret of Laboratoire d’Ethologie Expérimentale et Comparée, France.
Another macrosmatic species (one with a highly developed sense of smell), honeybees possess highly sensitive olfactory antennal lobes. Debajit Saha’s research shows they can detect lung cancer using synthetic biomarkers (artificial human breath that contains cancerous odours). Neural activity in the honeybee antennal lobe changes in response to cancer and non-cancerous samples, distinguishing between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) with 88% accuracy.
Dr. Saha and his team aim to develop a diagnostic tool capable of detecting early-stage lung cancer—a disease that can currently only be detected at late stages. “The field is growing and ever-developing. Researchers are going back to mother nature and applying what we are learning from these animals,” Dr. Saha says.
The Indian scenario
With India still grappling with high rates of undiagnosed TB, especially in underserved areas, could ‘HeroRATS’ be a solution?
Tuberculosis specialists believe this may work. “The work of ‘HeroRATS’ sounds fascinating and can be looked at as a secondary means of diagnosis but whether it can be implemented in India or not, only the NTEP can determine,” says Dewraj Sarkar, District TB Officer, Darjeeling, West Bengal.
Rajendra Kumar, State TB Officer of Chandigarh believes integrating rat-based TB detection into the NTEP could significantly enhance case detection, particularly among children and smear-negative patients. “The cost-effectiveness, speed, and accuracy of trained African giant pouched rats make them a viable secondary screening tool in high TB-burden areas,” he says. A phased approach, starting in select high-TB burden areas and States, followed by controlled expansion, could ensure feasibility and effectiveness, he adds.
“If the Central TB Division takes the initiative to collaborate with APOPO and implement the programme, it will help high-burden states like Maharashtra to detect cases faster,” says Sandeep Sangale, STO of Maharashtra.
Dr. Agizew says he hopes to revive discussions that were interrupted by the COVID-19 pandemic, to introduce these trained rats to India as secondary diagnostic tools, pointing out that this collaboration could significantly accelerate diagnosis, save lives and perhaps support the country’s efforts to eradicate TB.
(Neelanjana Rai is an independent journalist covering global health, indigenous communities, innovations and environmental issues. neelanjana189@gmail.com)
Published – February 28, 2025 05:00 am IST
