Living With Tuberculosis: How to Avoid Complications

Could African Giant Pouched Rats Offer A Solution To The Challenges Of TB Diagnosis?

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 monthsPhoto 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 longerPhoto 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

Fight TB With Early Detection

As we observe TB Awareness Month, professional nurse Tsholofelo Mafafo from Boksburg North Clinic shares crucial insights into the symptoms, causes and importance of early detection of TB as it remains one of the deadliest infectious diseases globally, claiming millions of lives annually.

What is TBTB is a serious illness that mainly affects the lungs. The germs that cause tuberculosis are a type of bacteria.

It can spread when a person with the illness coughs, sneezes or sings. This can put tiny droplets with the germs into the air. Another person can then breathe in the droplets, and the germs enter the lungs. Tuberculosis spreads easily where people gather in crowds or where people live in crowded conditions.

Symptoms of TBMafafo highlights that TB symptoms include coughing, unexplained weight loss, drenching night sweats, fever and loss of appetite.

"These are the primary indicators, though other symptoms may also occur.

"Notably, some individuals can have TB without displaying any symptoms. Which is why it is crucial to test regularly, especially for those with chronic conditions like hypertension, diabetes, HIV, epilepsy, or asthma."

Tumisho Phosa and Tsholofelo Mafafo.

She said people with compromised immune systems, such as those with diabetes, are more susceptible to TB.

"Early testing is crucial to catch the disease before it progresses."

Mafafo stresses that TB is curable but can be fatal if left untreated.

"It is essential to seek medical attention early and avoid self-diagnosis."

Tsholofelo Mafafo.

Also Read: St Francis commemorates World Aids Day

The nurse noted a decrease in stigma surrounding TB, as people now understand its contagious nature and the risks of reinfection leading to drug-resistant TB.

"I encourage individuals to get tested, have their families tested, and adhere to treatment regimens. Preventive measures such as frequent handwashing and seeking medical care if symptoms persist are also fundamental."

Message for TB awareness month

In line with the global theme "Yes! We Can End TB: Commit, Invest, Deliver," Mafafo's message is clear: early detection and treatment are key to combating TB.

Tsholofelo Mafafo explaining to Tumisho Phosa about the importance of early detection.

By committing to action, investing in healthcare, and delivering high-quality care, we can collectively work towards ending this epidemic. As TB continues to affect millions worldwide, awareness and proactive measures are more critical than ever.

Call to action:1. Get tested: Regular testing is vital, especially for those with chronic conditions.

2. Comply with treatment: Adhere to treatment regimens to prevent drug resistance.

3. Prevent spread: Practice good hygiene and seek medical care if symptoms persist.

Also Read: World Tuberculosis Day: TB and children

   

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First Doses Announced In Phase 2 Trial For TB Vaccine Candidate

Spanish biopharmaceutical company Biofabri and nonprofit scientific research organization IAVI announced today that the first doses of tuberculosis (TB) vaccine candidate MTBVAC have been administered in a large-scale safety and efficacy clinical trial.

The phase 2b IMAGINE (Investigation of MTBVAC toward Accelerating Global Immunization for a Neglected Epidemic) trial, sponsored by IAVI, will test the safety and efficacy of the live-attenuated, single-shot TB vaccine candidate in roughly 4,300 participants with latent TB in 15 sites in Kenya, Tanzania, and South Africa. The trial's first participants received doses on February 19 and will be followed up for 2 to 3 years. 

MTBVAC is one of 16 TB vaccine candidates currently in clinical trials. The only licensed TB vaccine is the bacilli Calmette-Guerin (BCG) vaccine, which has been around for more than 100 years. Although the BCG vaccine is effective at preventing severe TB in children under 5, it offers poor protection against TB disease in adults and adolescents. 

"The IMAGINE trial is an important new effort to develop a vaccine capable of combatting the world's deadliest disease," Lewis Schrager, MD, head of IAVI's TB vaccine development efforts, said in a press release. "Because MTBVAC is a single-shot vaccine, we are hopeful that, if proven effective, MTBVAC could prevent millions of cases of TB disease, particularly in persons living in some of the world's most difficult-to-reach locations."

MTBVAC is being developed as both a more effective and longer-lasting vaccine than BCG for newborns and for preventing TB in adolescents and adults. The vaccine has demonstrated comparable or favorable immunogenicity and safety profiles compared with BCG in phase 2 trials in newborns and adults. It's also being evaluated in a phase 3 trial in newborns in South Africa, Madagascar, and Senegal and in a phase 2a trial in people with and without HIV.

Global toll of TB highlights need for an effective vaccine

According to the most recent global TB report from the World Health Organization (WHO), 10.8 million people globally contracted TB in 2023, and 1.25 million died from the disease. TB cases and deaths occur primarily in low- and middle-income countries (LMICs).

The MTBVAC trial's principal investigator added that, in addition to being the leading infectious disease killer globally, TB has a wide-ranging impact on high-burden countries.

"Besides the millions of resultant deaths, TB is also associated with substantial reductions in the gross domestic product of low- and middle-income countries, given that economically active young people are often affected by the disease," said Keertan Dheta, MBBCh, PhD, of the Centre for Lung Infection and Immunity at the University of Cape Town. "Even after effective treatment patients often suffer lung damage and scarring, and thus TB is the most common and important cause of lung disability in many TB endemic countries."

The global toll of the disease has prompted the WHO to push for development and distribution of a TB vaccine that is affective in all age-groups. In a 2022 report that called for more international funding for TB vaccine development, the WHO estimated that a vaccine that was 75% effective could avert up to 110 million new TB cases and as many as 12.3 million TB deaths from 2025 to 2050.

Ensuring global supply

MTBVAC was designed by researchers at the University of Zaragoza in Spain and France's Institute Pasteur and developed by Biofabri. If MTBVAV demonstrates safety and efficacy, IAVI and Biofabri say they will work together to ensure a sufficient, affordable supply of the vaccine is available in LMICs.

"Biofabri and its partners in Asia and South America will work together to help ensure a global supply of the vaccine," said Biofabri CEO Esteban Rodriguez.

The news comes amid uncertainty about the potential impact that the US Agency for International Development (USAID) funding freeze will have on global TB treatment, diagnosis, and prevention efforts. USAID is the leading bilateral donor for global TB control efforts, accounting for roughly one third of international donor funding for the disease.

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