10 Benefits of Having a Dog, According to Scientific Research
Plant Compound Used In Traditional Medicine May Help Fight Tuberculosis
A compound found in African wormwood -- a plant used medicinally for thousands of years to treat many types of illness -- could be effective against tuberculosis, according to a new study that is available online and will be published in the October edition of the Journal of Ethnopharmacology.
The team, co-led by Penn State researchers, found that the chemical compound, an O-methylflavone, can kill the mycobacteria that causes tuberculosis in both its active state and its slower, hypoxic state, which the mycobacteria enters when it is stressed.
Bacteria in this state are much harder to destroy and make infections more difficult to clear, according to co-corresponding author Joshua Kellogg, assistant professor of veterinary and biomedical sciences in the College of Agricultural Sciences.
While the findings are preliminary, Kellogg said the work is a promising first step in finding new therapies against tuberculosis.
"Now that we've isolated this compound, we can move forward with examining and experimenting with its structure to see if we can improve its activity and make it even more effective against tuberculosis," he said. "We're also still studying the plant itself to see if we can identify additional molecules that might be able to kill this mycobacterium."
Tuberculosis -- caused by the bacteria Mycobacterium tuberculosis, or Mtb -- is one of the world's leading killers among infectious diseases, according to the Centers for Disease Control and Prevention. There are about 10 million cases a year globally, with approximately 1.5 million of those being fatal.
While effective therapies exist for TB, the researchers said there are several factors that make the disease difficult to treat. A standard course of antibiotics lasts six months, and if a patient contracts a drug-resistant strain of the bacteria, it stretches to two years, making treatment costly and time consuming.
Additionally, the bacteria can take two forms in the body, including one that is significantly harder to kill.
"There's a 'normal' microbial bacterial form, in which it's replicating and growing, but when it gets stressed -- when drugs or the immune system is attacking it -- it goes into a pseudo-hibernation state, where it shuts down a lot of its cellular processes until it perceives that the threat has passed," Kellogg said. "This makes it really hard to kill those hibernating cells, so we were really keen to look at potential new chemicals or molecules that are capable of attacking this hibernation state."
Multiple species of the Artemisia plant have been used in traditional medicine for centuries, the researchers said, including African wormwood, which has been used to treat cough and fever. Recent studies in Africa have suggested that the plant also has clinical benefits in treating TB.
"When we look at the raw plant extract that has hundreds of molecules in it, it's pretty good at killing TB," Kellogg said. "Our question was: There seems to be something in the plant that's really effective -- what is it?"
For their study, the researchers took raw extract of the African wormwood plant and separated it into "fractions" -- versions of the extract that have been separated into simpler chemical profiles. They then tested each of the fractions against Mtb, noting whether they were effective or ineffective against the bacteria. At the same time, they created a chemical profile of all of the tested fractions.
"We also used machine learning to model how the changes in chemistry correlated with the changes in activity that we saw," Kellogg said. "This allowed us to narrow our focus to two fractions that were really active."
From these, the researchers identified and tested a compound that effectively killed the bacteria in the pathogen's active and inactive states, which the researchers said is significant and rare to see in TB treatments. Further testing in a human cell model showed that it had minimal toxicity.
Kellogg said the findings have the potential to open new avenues for developing new, improved therapeutics.
"While the potency of this compound is too low to use directly as an anti-Mtb treatment, it may still be able to serve as the foundation for designing more potent drugs," he said. "Furthermore, there appear to be other, similar chemicals in African wormwood that may also have the same type of properties."
The researchers said that in the future, more studies are needed to continue exploring the potential for using African wormwood for treating TB.
Co-authors from Penn State are R. Teal Jordan, research technologist and lab manager in veterinary and biomedical sciences, and Xiaoling Chen, graduate student in pathobiology. Also co-authors on the paper were Scarlet Shell, Maria Natalia Alonso, Junpei Xiao, Juan Hilario Cafiero, Trevor Bush, Melissa Towler and Pamela Weathers, all at Worcester Polytechnic Institute.
The National Institutes of Health's National Institute for Allergies and Infectious Disease and the U.S. Department of Agriculture's National Institute of Food and Agriculture helped support this work.
Molokai Ranchers Worry Herds Will Take A Hit Amid Bovine TB Outbreak
Molokai ranchers and farmers are losing livestock due to an outbreak of bovine tuberculosis, the most severe spread of the disease that officials have seen in decades.
Six different herds of cattle, swine and sheep have been found infected with the disease between June and March in the central and west ends of Molokai, with several groups being depopulated or slaughtered.
"We've raised, like, really nice hogs and it's a real disappointment and upset me that this whole thing is happening. I'm devastated," Susan Donnelly, who lives on Molokai's west end, said Monday night after losing cattle, sheep and pigs earlier this year. "The whole farm got depopulated, we lost everything. Everything. We killed everything."
Cattle are the primary host of the bacteria that causes bovine tuberculosis, according to the state Department of Agriculture, but it can also infect other domesticated animals, such as sheep, goats, pigs, dogs and cats, and wild species like boars and deer.
The cause of the infections remain under investigation, Dr. Jason Moniz, veterinary program manager for the Department of Agriculture's Animal Disease Control Branch, said during a department meeting on Molokai Monday night. He added that research into the wildlife around Hoolehua and Mapulehu "is important to complete."
"We are concerned that this outbreak is big enough that if we are not careful, we could end up jeopardizing the status of the whole state and potentially other states because we do move cattle from this state, including Molokai, to other states," Moniz said. "This outbreak appears to be highly contagious, substantial and widespread, and may have multiple sources."
A quarantine order was issued for Molokai on April 8 to require a permit before moving any live ungulates, except horses, to any location outside their premises due to detections of bovine tuberculosis, which is a chronic and transmissible bacterial disease of animals.
Moniz reassured that any meat from cattle, swine or deer that pass the U.S. Department of Agriculture Food Safety and Inspection Service inspection at slaughterhouses are OK for human consumption.
Those who attended the meeting in person at the Lanikeha Community Center in Hoolehua on Monday night were concerned with the department's response, saying that quarantine and depopulation methods would literally "kill Hawaii's cattle industry" and have severe financial impacts on ranchers and farmers.
Others questioned why the department was only responding to the issue now, arguing that there was very little communication with the public previously and wanting to meet again for other possible solutions and clarifications.
"There's a lot of work to be done and I hear the frustration, I understand what's going on with the producers," said department veterinarian Dr. Isaac Maeda. "This is not anything that is simple. Kind of like Dr. Moniz is saying, we cannot be doing the same thing. We have to try and do something different."
The meeting lasted beyond two hours while residents also asked about possible sources of the infectious spread, including the uncontrolled axis deer or rodents, the importation of feed or the ongoing drought conditions.
Though low numbers of mongoose, feral pigs and axis deer have tested positive for bovine TB on the east end of Molokai in the past, their role in this particular outbreak is yet to be determined and needs more proof, Moniz said.
"I'm so glad that you guys, for the benefit and safety of the people, are going to test feral animals," said Jimmy Duvauchelle, who worked for Molokai Ranch for 50 years. A herd at the ranch is being considered for depopulation, or test and removal, to eliminate infection.
Bovine TB on Molokai
Historically, bovine tuberculosis on Molokai is more prevalent in feral pigs, Moniz said. In 1985, a complete island depopulation of more than 9,000 beef cattle was conducted, because at that time, it was thought that infection in wildlife would die out once infected cattle herds were removed.
Beef operations halted in 1986 while the island remained cattle-free, but slowly repopulated with steers thereafter. When all the steers were slaughtered and found free of bovine TB, breeding cattle that tested negative for the disease were allowed to be restocked.
During a wildlife surveillance survey on Molokai from 1998 through 2012, 20 infected feral swine were detected between Kamalo and Mapulehu. None of the samples from 477 axis deer, 81 feral goats or 61 mongoose tested positive.
No positive cases were detected in 25 years of annual herd tests on the east end from 1997 to 2021.
In addition, cattle slaughtered at the Molokai Cooperative Slaughter Plant or any other plant throughout the state are routinely inspected for bovine TB lesions.
In June, however, a new outbreak of bovine tuberculosis was detected in a small beef herd in central Molokai. Testing of a neighboring herd found they were also infected.
Moniz said that both infected herds were depopulated after ranch facilities were cleaned and disinfected. The quarantine orders placed on those herds ended on Dec. 22.
In November, four swine from a farm on the west end of Molokai were found positive for bovine TB when slaughtered. The premises where the swine lived also contained cattle and sheep.
The ranch was placed under quarantine and depopulated, he said. Other swine farms that were traced in central Molokai are also quarantined and depopulation is being planned or is ongoing, Moniz said.
Recently in January to March, more infected herds were detected in both the central and west end of Molokai.
Similar to testing for COVID-19 variants, Moniz said that genome sequencing has helped to provide insight to the bovine TB clusters on Molokai, such as the fact that all detections in the 2021-22 outbreak are of the Molokai strain, meaning it's not caused by a new introduction from outside of the island.
However, sequencing shows that there may be three separate outbreaks on Molokai with different sources/introductions, he said.
And, looking at each swine and cattle herd recently testing positive for bovine TB, there are several indicators that suggest some infections happened over a long period of time, some very recently, or they contracted the disease all at the same time.
Combating the spread
Officials said they are still working to determine the extent of the outbreaks in livestock and hope to expedite bovine TB testing, contact tracing and depopulation of infected herds; ramp up testing of hunter-collected wildlife carcasses; and schedule testing for current infected herds and herds located within a 10-mile radius of infected herds.
"We're going to end up basically testing the whole island," Moniz said.
At the same time, the department is also seeking legislative funding for two positions, including a veterinary medical officer to lead disease investigation and control activities on Molokai full time and a full-time livestock inspector to assist with livestock testing, movement control and wildlife surveillance.
Funds are also being sought for a portable office to house two livestock inspectors and one vet, as well as to purchase a quarantine facility for handling and testing livestock and to support small farmers and ranches that do not have their own corrals.
They would also want funds to purchase feed for producers when conducting herd tests; a vehicle to move staff, equipment and livestock and buy an additional portable chute and livestock trailer.
"We know the herds that are infected, but we don't know the status of some of the other herds and it seems like the more we look, the more we're finding right now," Moniz said. "The purpose is to prevent the spread of bovine tuberculosis to the rest of the state, the nation and to the rest of the ranches on Molokai that are not infected."
* Dakota Grossman can be reached at dgrossman@mauinews.Com.
Does This Rhino Have Tuberculosis? Now There Is A Simple Test
White rhinoceros tend not to display symptoms of bTB for many years after infection.Credit Dr Peter Buss
The survival of white rhinos hangs in the balance. As well as poaching, habitat loss and climate change, they are also threatened with bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. Bovis). Cattle imported to South Africa in the 1880s brought bTB to South Africa. In the Kruger National Park, the infection was first identified in buffalo herds in the 1990s and has since been detected in 15 other species, including rhinos, cheetahs and lions1.
"It's now endemic," says Sven Parsons, a research veterinarian with Afrivet. "It is well established in many species."
The presence of M. Bovis in wildlife populations adds another challenge to conservation programmes, which heavily depend on animal relocation. "The Kruger National Park has historically exported rhinos to repopulate other protected areas or enhance the genetic diversity of other populations," says Parsons, who conducted this work while at the University of Stellenbosch in South Africa. "Being able to declare an animal free of infection plays a very important part in these efforts."
Until recently, conservationists lacked suitable tools for assessing the bTB status of rhinos. But a unique collaboration between wildlife researchers in South Africa and Mabtech, a Swedish biotechnology company specializing in monoclonal antibodies, has brought a solution.
The challenge of bTB detection
A blood sample, taken from the ear of an immobilized white rhino, is enough for Michele Miller (in the centre of the kneeling group) to now determine if the animal has bTB.Credit: Dr Peter Buss
South Africa's national and private game parks, along with the expansion of wildlife ranches, have increased the risk of bTB transmission between livestock and wildlife."It's a multi-host disease," says Michele Miller, a wildlife veterinarian and expert in animal infectious diseases at the University of Stellenbosch, who lives and works in the Kruger National Park. "If it's not identified and managed, it can spread to other species — including other wild animals, domestic animals and potentially even to humans if they come into contact with infected animals and don't take suitable precautions."
It is difficult to know how bTB affects the overall health of wild rhinoceros. Evidence suggests they are infected for many years before developing any clinical signs of the disease. But infection does create a significant challenge for conservation efforts.
"In the Kruger National Park, quarantine is currently imposed on rhino populations," says Parsons. "That means rhinos can't be moved to other locations without testing, to ensure they do not spread the disease elsewhere."
Rhinos at the park are held in secure pens while they undergo bTB testing over a three-month period. Only if the animal has negative test results can it be safely relocated. But methods of detecting the infection in other species have been deemed unreliable for rhinoceros.
A blood-based assay
Miller and Parsons set out on a mission to develop alternative screening tools that could easily and reliably detect bTB in rhinoceros. They looked towards the interferon-gamma release assay (IGRA), a blood test initially developed to diagnose bTB in cattle. It works by measuring the levels of interferon-gamma (IFN-γ), a molecule released by certain immune cells, after stimulation with M. Bovis proteins in a blood sample.
"The approach is fairly standard," says Parsons. "It's a very established diagnostic protocol."
"Monoclonal antibodies are versatile tools used to capture and detect small molecules originating from the body," says Niklas Ahlborg, an immunology expert and senior advisor at Mabtech. "They have several applications but are often used to measure compounds in the blood."
Mabtech specializes in the development of immunoassays for detecting or measuring specific compounds produced by the immune system. While the company had monoclonal antibody pairs available for detecting IFN-γ in several different species, these were mainly for animals used in research; it did not have specific antibodies for rhinoceros. However, given the evolutionary conservation of many proteins, it was possible that a kit developed for a closely related species might be effective.
"Rhinos fall into the same taxonomic category as horses," says Miller. "So that seemed like our best option."
Miller and Parsons explored the Mabtech equine IFN-γ ELISA Pro kit for use as part of a potential IGRA assay for diagnosing M. Bovis infection in white rhinoceros2. After reading their publication, Mabtech contacted the researchers to offer support.
"They were very eager to help us," says Miller. "In particular, when we were testing the antibodies for the rhinoceros assay, there was an additional step that was necessary. They went the extra mile and performed that step for us, helping standardize and ensure the high quality of the reagents we were working with."
It turned out that rhinos were only the start. Miller has discovered that Mabtech's cow kit can be used to detect bTB in African buffaloes3, and its domestic cat kit can be used in cheetahs4 and lions5. Josephine Chileshe, who helped Miller and Parsons develop the test as part of her PhD, is endeavouring to develop a similar diagnostic test for bTB in Canadian bison.
"In many wildlife projects, we often have to make our own reagents in-house, which is a costly and time-consuming process," says Miller. "Using a validated test with commercially available reagents and stringent quality control increases our confidence in the results."
Fruitful collaboration
Josephine Chileshe collects a blood sample to test.Credit: Prof Michele Miller
Partnerships between academics and companies in niche fields like wildlife health can be challenging due to limited commercial opportunities.
"Our experiences of working with Mabtech have been very positive," says Parsons. "They've been very eager to help us, not just by providing kits, but also offering their hands-on expertise."
This remarkable collaboration highlights the crucial role that cutting-edge diagnostics play in preserving the biodiversity of South Africa and beyond. Thanks to the development of these simple and reliable blood tests for btB, scientists and veterinarians can now easily detect the infection in various wildlife species, supporting conservation initiatives around the world.
"From a purely academic perspective," Parsons concludes, "working from the molecular level all to the way through to an ecological level is very rewarding."
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