Late one night in April 2013, UK veterinarian Jonathan Cranston woke in agony. There was a sharp pain shooting through his chest.
“I felt like I’d been stabbed,” he said. The pain soon passed, however, and he went back to sleep. “I didn’t think much of it.”
But that would not be the end of his ordeal.
In the weeks that followed, the stabbing pain didn’t return, but it was replaced with night sweats, shortness of breath, coughing and weight loss. “I started deteriorating quite quickly,” he said.
He was soon diagnosed with pneumonia and promptly given antibiotics. But the drugs didn’t work — and his long road to a true diagnosis began.
An animal source
A few months earlier, Cranston had been working with a private veterinary organization in the town of Nelspruit, located in the province of Mpumalanga, South Africa. He declined to give the name of the group.
Cranston had worked with the organization for a few weeks each year, part of a team passionate about improving the health of the rhinoceros and other wild animals in that region.
“We worked with everything from rhinos to lions to giraffes. The complete range,” he said, adding that this was far removed his regular role working with domestic animals in the UK.
On the 2013 trip, one group of animals had dominated his time. “We were predominantly doing work with wildebeest,” he recalled. His team had been monitoring the animals’ vital signs to learn how they cope in an enclosure.
Cranston had, in fact, spent large quantities of time head-to-head with one particular wildebeest that would later become known — in his head, at least — as patient zero.
He suspects that this animal was infected with bovine tuberculosis, caused by the bacteria Mycobacterium bovis, because Cranston himself was diagnosed with this infection months later.
Bovine TB, also known as zoonotic TB, can infect any animal. Its symptoms resemble those of the more regular form of TB seen in humans, which is caused by Mycobacterium tuberculosis.
In 2015, there were an estimated 149,000 cases of humans infected with zoonotic TB, mostly in Africa and South Asia, and more than 13,000 deaths.
‘I knew something was wrong’
“Thinking back, that trip I was predominantly at the head end of the wildebeest,” he said, recoiling a little at the memory. His hand had been in and out of the animal’s mouth to ensure a clear airway when it was anesthetized. This intimate contact exposed him to particles in the animal’s respiratory tract, its bloodstream and many other bodily fluids and cavities that could harbor infections of all forms.
When he got sick in 2013 and doctors initially failed to figure out what was wrong with him, this vision plagued his mind.
“To all these doctors, I was an anomaly,” he said. “But I knew something (else) was wrong.”
After being incorrectly treated for pneumonia, he collapsed at work and was admitted into the hospital.
“By the time I was in hospital, I was pretty sure it was TB,” he said, though none of his doctors thought the same. “If it wasn’t TB, I was confused what it could be.”
For Cranston, bovine TB was an occupational hazard that was never really highlighted as a concern during his time at veterinary school in the UK, where the infection is rare, though concern has been raised more widely in the UK about infected badgers and cows. He knew that animals could harbor the disease and that he had not been in contact with humans infected with TB during his time in South Africa.
But still, zoonotic TB was not on his physicians’ radar.
After 12 weeks of testing and attempts at treatment, lab cultures provided the diagnosis — and treatment — he had been waiting for. “I felt vindicated when I got the diagnosis,” he admitted.
But for many others around the world, this diagnosis is never made.
The reality of zoonotic TB
“He is the poster child for why you need to know it’s (Mycobacterium) bovis and not (human) TB,” said Dr. Paula Fujiwara, scientific director of the International Union Against Tuberculosis and Lung Disease, who raised concerns over this form of TB during her organization’s annual conference in Liverpool last week. “He was misdiagnosed … and he could have developed multidrug-resistant TB.”
Prescribing the wrong antibiotics and prolonging the delivery of effective treatment for TB are factors that fuel drug resistance, “so he had to take medications for a lot longer.” Cranston ended up requiring a year of treatment.
Fujiwara is advocating for greater recognition of zoonotic TB worldwide, and her organization brought attention to it during a meeting of the Strategic and Technical Advisory Group for TB at World Health Organization headquarters in Geneva in June. A road map is now being developed to tackle the issue and reduce the number of new cases.
In 2015, the WHO established the End TB strategy, which aims to reduce current numbers of TB infections among humans — in all forms — by 90% by 2035. Fujiwara believes that animals need to be part of the plan to get there, as both regular and bovine TB contribute to the total numbers cases reported each year. It’s different bacteria but the same disease.
“If you don’t deal with (this) source — the animal — you won’t get to the end of human TB,” she said.
Tuberculosis was estimated to infect more than 10 million people globally in 2015 and cause 1.8 million deaths, making it the leading cause of death from infectious disease.
Zoonotic forms of TB among humans have significantly lower numbers, representing just 1% of total infections.
But experts believe those numbers are vastly underreported.
“The problem is that the amount of information is scanty,” said Dr. Mario Raviglione, director of the Global TB Programme at the WHO.
In addition, the majority of health clinics don’t look for this form of TB. Many of those that do lack the right equipment to diagnose it. Unlike regular TB, which can now be diagnosed with rapid tests, bovine TB requires culturing samples for up to eight weeks.
“You need more sophisticated tests, and that is more costly,” Raviglione said. “Many places do not have diagnostic capacity.”
Bovine TB also requires a slightly different treatment regimen. Regular TB treatment begins with four antibiotics prescribed for two months, followed by two for another four months. But the bacteria behind bovine TB are resistant to one of these antibiotics — pyrazinamide — meaning other types may need to be prescribed for effective treatment.
Where, and how, it occurs
More than 60% of zoonotic TB cases are estimated to occur in Africa, according to Raviglione, with South Asia being the next on the list. These are regions where large numbers of people live in close proximity to animals, such as livestock, and consume raw milk — and occasionally raw meat — from them.
“Unpasteurized milk is the common way zoonotic TB gets into humans,” Raviglione said.
Symptoms are similar to those of regular TB, making it hard to diagnose, but it has greater potential to spread from the lungs into other body parts such as the lymph nodes and gastrointestinal tract.
Though this form of TB is predominantly linked to cows, any animal can become infected — including elephants, lions, giraffes and wildebeests. But their likelihood of spreading infection is lower, because “these animals do not come in contact with humans or produce milks that humans consume,” Raviglione said.
But for Cranston and his wildebeest, such contact was inevitable and therefore an occupational hazard.
Butchers and people who work in slaughterhouses are also considered to have jobs that put them at risk, and Fujiwara wants these key groups to be recognized — and targeted.
Ending animal transmission
The WHO is now working with the anti-tuberculosis union to put together a road map to tackle this route of infection globally.
“We need to build better evidence that will allow us to intervene,” Raviglione said.
Fujiwara is calling for greater surveillance of cases as well as appropriate diagnostics. “If we can understand the information, we can develop the appropriate tools and treatment regimens,” she said. “It’s part and parcel of the whole fight against tuberculosis.”
But Fujiwara also highlighted the need for greater awareness among those at risk and, in the case of Cranston, better communication between doctors and patients.
“The basic lesson is to listen to your patient,” she said.
As for Cranston, now 35, he was given the all-clear in 2014 and continues to work in South Africa each year.
“I went out in August the following year,” he said, adding that he stood clear of the animals at first and watched from a distance. But he soon grew back his confidence.
“I’m definitely much more cautious of what I do and get involved in,” he said. “But at the same time, there is a risk that I’m prepared to take.”