The interconnected, growing threat of TB in animals and humans

Old problem, new challenges

It is believed that bovine TB was brought to South Africa by colonial settlers importing infected cattle in the 19th century. “Primarily, it has been a disease among domestic cattle,” Miller says. “It is only since the 1990s that we’ve really been aware that it can spill over from domestic animals into wildlife in the KNP.”

Centuries ago, as high as 20% of human cases of TB were caused by transmission from cattle, primarily via unpasteurised milk. This is one of the reasons why TB is, today, an actively controlled disease among animals. “Although surveillance and monitoring programmes have reduced TB prevalence in cattle, animal TB is rearing its head again,” Miller says.

Several factors determine whether a population can maintain and spread animal TB infection. These include the presence of enough susceptible hosts, how long the bacterium infects its hosts without killing it (often dependent on the status of the host animal’s immune system), and whether the bacteria can remain viable long enough to find new hosts.

Although animals are typically infected with M. bovis and humans with M. tuberculosis, reports are increasingly noting reverse infections from animals to humans and vice versa, Miller says. “There is a gap in our knowledge as to what’s leading to these infections jumping between species.

“What we are seeing is that in a wildlife park, M. bovis crosses the border from buffalo herds to goats and cattle, to soil and water, and subsequently to humans," she says. “People with a high TB burden who, for example, care for captive elephants can also spread human TB to these animals.”

Route(s) of transmission 

In a multiple-host system such as the KNP, there are many routes for transmitting TB among or between wildlife species.

Some species are considered important “reservoir” hosts of TB, which means they maintain the infection within their population and spread the disease to other species. While not all of these reservoir hosts, such as buffalo and greater kudu, exhibit signs of disease, get sick or perish, the existence of many of them ensures that infections persist within the park’s ecosystem. On the other hand, “accidental” or “spillover” hosts typically contract TB through contact with a reservoir host.

Indirect spread may occur through contact with the mycobacteria in the saliva, nasal mucus, faeces, or urine of infected animals. This method of transmission usually occurs through close contact between individual animals, particularly in social species like African buffalo.

Moreover, M. bovis in animals’ respiratory secretions can contaminate the environment since the pathogen is able to survive in moist soil in water holes and mud wallows. This may lead to its transfer between buffalo or to other species. (The prevalence of animal TB in buffalo is estimated to range up to 40% in some areas of the KNP).

Although the mechanisms of transmission between herbivores such as antelope and rhinos are still poorly understood, they also relate to indirect interaction through the sharing of resources such as contaminated water holes and to the consumption of infected vegetation.

Carnivores and scavengers, on the other hand, can be infected by eating infected prey. In addition, African lions have been found to transmit M. bovis through biting, causing infection in other lions.

Recent evidence also suggests that lions and African wild dogs are shedding M. bovis in airborne particles through their respiratory secretions, Miller says.

Wild animals kept captive in zoos, on game farms, and on wildlife ranches can also contract the disease. These infections can be caused by transmission within or between species due to the presence of infected animals or their human caretakers.

Together, these and other transmission pathways enable TB bacteria to survive and spread among wildlife species.

“We are finding that TB bacteria are really, really hardy,” Miller says. “They can remain alive in soil or around water holes for days to months, depending on the conditions.” (Mycobacteria possess a unique, thick lipid cell wall that allows them to not only survive in harsh environmental conditions but also resist the immune responses of their hosts.)

In areas where domestic livestock and wildlife share grazing and water sources, there is a higher risk of spillover (pathogen transmission from animals to humans) and spillback (pathogen transmission from humans to animals) within the wildlife population.

Moreover, certain risk factors such as drought, increased population density, and animals clustering at artificial water and feeding sites can increase the likelihood of bovine TB occurrence in certain species. Interestingly, though, data collected in the KNP indicate that M. bovis-infected white rhinos that receive sufficient food and water appear to be able to contain the disease (that is, suppress the infection, despite the bacteria remaining present in their bodies).

SU researchers leading the pack

SU’s Animal TB Research Group is at the forefront of advances in understanding TB infections in wildlife.

Scientists in the group have reported research showing that the critically endangered African wild dog population in the KNP has a high apparent prevalence of M. bovis infection (82%), with associated mortalities.

In 2022, the group and its research collaborators showed that about one in every seven rhinos in the park was infected with M. bovis. Their findings indicated an estimated prevalence of bovine TB infection of 15,4% across black and white rhino populations.

A recent surveillance study investigating antibodies against M. tuberculosis complex antigens in elephants estimated the level of infection in the KNP’s population to be between 6% and 9%, suggesting that M. bovis and possibly M. tuberculosis infection are more common than previously thought.

The Animal TB Research Group is also part of a global consortium that recently received funding from the European Commission to expand genomics surveillance to include the main pathogens affecting people and animals in South Africa, Mozambique, and Kenya.

This SU-led consortium aims to increase the use of genomic epidemiology to address public health issues such as TB, HIV-1, and antimicrobial resistance in these three countries. The consortium will use a “One Health” approach to conduct early-warning testing in wastewater, and animal surveillance to detect emerging pathogens.

The Animal TB Research Group is leading the consortium’s work on environmental and animal sources of TB. This includes investigating the role of host genetics and immunology in animals’ susceptibility to bovine TB, the genetic diversity of pathogens and their impact on wildlife and livestock, and the development of diagnostic assays for different host species.

One Health approach

South Africa is one of the countries experiencing significant problems around human and animal TB, starting with its diagnosis. SU has a wide portfolio of TB expertise, ranging from that in microbiology, vaccine testing, drug development, and immunology to genetics.

The Animal TB Research Group’s specific focus is the immunology, epidemiology, management, and control of TB in animals, as well as aspects that impact the human-animal interface. The group has adopted the integrated, collaborative, multisectoral, and transdisciplinary One Health approach, which aims to sustainably balance and optimise the health of people, animals, and ecosystems.

Since both animal and human TB can spread across the species boundaries, it is crucial to employ this approach when it comes to detecting, understanding, and controlling TB.

A key area of research in the group is the development of molecular and cellular techniques for detecting infection in animals. This is important, given that bovine TB not only has a severe impact on the health of animals but also has major economic implications.

Many rural communities depend on cattle as a source of meat and milk, and livestock agriculture is the economic lifeblood in many areas. If an infection is detected on a given farm, the farm will be placed under quarantine by agricultural authorities, and the owner will not receive state compensation for the slaughtered animals. This can have a significant impact on livelihoods and food sources, particularly at the household level.

Miller says infected animals in South Africa are slaughtered rather than treated to avoid creating drug-resistant strains of the pathogen. “M. bovis is already naturally resistant to one of the key drugs used for treatment in people.

“The other reason is that we don’t want to keep infected animals that can continue to transmit the disease around. So, generally, when you have a TB control programme for cattle, infected animals are culled to break the cycle of transmission.”

Repurposing existing technology

Researchers in the group have successfully developed various in vitro TB diagnostic immunological blood assays, DNA tests for detecting TB directly, and a novel mycobacterial culturing method for enhancing the growth of bacteria from difficult-to-culture respiratory samples.

The group has been modifying techniques originally used for human TB diagnostics, including a culture-independent rapid polymerase chain reaction (PCR) test used in human TB clinics. “This has been a wonderful piece of technology that can be used as a rapid screening tool across wildlife species,” Miller says. “The technology enables us to run the tests and get the results within a couple of hours.”

SU’s researchers have also considered how existing diagnostic tools for TB can be used in the routine screening of leopards and other wild felids. “We have known for years that lions can get TB,” Miller says. “We have done a lot of research on trying to develop blood-based tests that can identify infected lions. We’ve shown that some of these tests that we’ve developed for lions can be used for cheetahs and across the big cat species. That’s been a real breakthrough because we didn’t have a leopard or cheetah test before.”

SU is taking testing to another level by looking at the epidemiology of the disease. “What’s interesting is that different animals have different levels of resistance to M. bovis,” Miller points out.

She says her team has not been investigating drug resistance in the M. bovis bacteria specifically. “What we are seeing, however, is that over time, the prevalence of animal TB in the KNP and particularly in buffalo is slowly increasing.

“We are looking at the population and systems level, trying to understand what it takes for the immune systems of some animals to clear infection, whether it is minimising animal density or purely genetics.

“This comparative biology enables us to investigate why, sometimes, when an animal gets exposed to TB, it doesn’t develop the disease or, if it does develop the disease, it doesn’t die.

“For instance, we believe that healthy rhinos in the KNP system, not in drought years but in a normal [rainfall] cycle, are fairly resistant to developing the disease. We are now following infected animals and getting samples to see if they can clear infections over time.”

New frontiers

The Animal TB Research Group is using the KNP system as a model to figure out what happens when different infected species interact with each other and with their environment, Miller says. “This can serve as a model for us to go into communities, especially rural communities, where livestock and humans also live in close contact.” The team is also doing work on environmental samples taken from communities living close to protected areas, primarily in KwaZulu-Natal.

“There are literally no statistics about TB in humans caused by M. bovis in South Africa,” Miller points out. “So, we don’t know how big a threat animal TB is to humans in our country.” Recently, SU researchers were involved in a pilot study, done in collaboration with the African Health Research Institute, which suggested that M. bovis DNA could be isolated from people in the area studied.

The researchers are applying surveillance techniques that were developed during the COVID-19 pandemic to track bovine TB in wastewater samples. This work, done in collaboration with the South African Medical Research Council, enables them to monitor a particular community or environment and could help them understand the transmission process and identify the potential downstream risk of TB contamination.

“The problem with TB is that it’s not a one-directional issue,” Miller emphasises. “If we don’t take care of the TB problem in our domestic animals and in our wildlife species, there will be potential spillover into humans, and that will add to the total TB burden.

“We have a unique situation here in the KNP, where [infected] animals are not being treated. What happens in a system when there isn’t intervention? We’re watching as this all unfolds.

“The fact that we have discovered infections in rhinos and elephants in the last seven years or so also suggests that TB is increasing in the environment and in wildlife populations.”