Tag Archives: tuberculosis

New vaccine shows protection against aerosol tuberculosis infection in monkeys

The new tuberculosis vaccine MTBVAC takes a new step as a candidate for universal vaccination against tuberculosis and an alternative to the current Bacillus Calmette–Guérin (BCG) vaccine, according to the results of the research published in the journal NPJ-Vaccines which shows the protection results of the MTBVAC vaccine compared to the current BCG vaccine in a model of respiratory tuberculosis in rhesus macaques.

The currently used BCG vaccine, based on a live attenuated form of Mycobacterium bovis isolated from cows and which, this year 2021, will make a 100 years since its first use in humans as a tuberculosis vaccine, continues to be the only licensed vaccine against the disease. After decades of research in this field, MTBVAC is the first and only vaccine based on the human pathogen Mycobacterium tuberculosis that has entered human clinical evaluation, a historic milestone in human vaccinology.

MTBVAC has shown its safety in Phase 1 studies in adults in Switzerland and in Phase 1b in newborns in South Africa, where Phase 2 studies are currently being carried out in tuberculosis-infected and uninfected adults and in healthy newborns to select the dose and study its safety and immunogenicity in a larger number of participants in order to support advanced Phase 3 efficacy evaluation in the target age-groups.

MTBVAC is the first and only live attenuated vaccine based on a human isolate of Mycobacterium tuberculosis designed and constructed by the research groups of Carlos Martin of the University of Zaragoza and of Brigitte Gicquel of Institut Pasteur in Paris

In this recently published study led by Dr. Sally Sharpe from Public Health England, a single dose of the MTBVAC vaccine administered intradermally has been found to confer significantly better protection against aerosol exposure to M. tuberculosis in Rhesus macaques when compared to BCG by the same route and dose of administration. Vaccination with MTBVAC resulted in a significant reduction in disease pathology induced by M. tuberculosis infection as measured by medical scan imaging in vivo, macroscopic pathological lesions examination, and pathological anatomy study of the frequency and severity of pulmonary granulomas.

This study consolidates previous preclinical and clinical safety and immunogenicity studies and represents a strong proof of concept of the efficacy of MTBVAC in the macaque model, the most relevant model of efficacy against respiratory tuberculosis, supporting and urging the clinical development of studies to demonstrate the efficacy of MTBVAC as a prophylactic vaccine against respiratory tuberculosis in humans. This would make MTBVAC an essential tool in the fight against tuberculosis.

Despite WHO’s declaration of tuberculosis as “global health emergency” in 1993, today the disease continues to be one of the leading causes of mortality caused by infectious diseases worldwide. The WHO Global tuberculosis report 2020 estimates that 1.4 million people died of tuberculosis in 2019 and it is estimated that as a consequence of the COVID-19 pandemic deaths from tuberculosis could increase by up to twenty per cent (20 %) in the next five years.

No evidence to support use of BCG vaccine against COVID-19

The BCG (Bacillus Calmette–Guérin) vaccine, discovered by Albert Calmette and Camille Guérin, is one of (if not) the most widely used vaccine worldwide. Next year will mark the 100th anniversary of the first time this live, attenuated (weakened) version of a virulent bovine strain of tubercle bacillus was administered to a person.

The BCG vaccine protects against tuberculosis, also known as TB, a serious infection that affects the lungs and sometimes other parts of the body, such as the bones, joints and kidneys. The World Health Organization (WHO) recommends BCG vaccination as soon as possible after birth in countries with a high incidence of tuberculosis

This century-old vaccine is in the spotlight the past weeks because of a few ecological studies (pre-prints, not peer-reviewed at this stage) that claim a strong correlation between BCG vaccination and protection against SARS-CoV2, the coronavirus causing COVID-19.

Ecological studies are inherently limited since they take aggregate data and try to make inferences at the individual level. Such ecological studies are prone to significant bias from many confounders, including differences in national demographics and disease burden, testing rates for COVID-19 virus infections, and the stage of the pandemic in each country.

Some of these analyses were done over a month ago. Since then, COVID-19 cases and deaths have spiked up in many low and middle-income countries where BCG vaccination is administered to all newborns. Many of the countries with BCG in their national immunization programs seriously under-test for COVID-19.

There is experimental evidence from both animal and human studies that the BCG vaccine has non-specific effects on the immune system. However, these effects have not been well characterized and their clinical relevance is unknown.

There are two registered protocols for clinical trials — BCG-CORONA (The Netherlands) and BRACE (Australia) — both of which aim to study the effects of BCG vaccination given to health care workers directly involved in the care of patients with COVID-19. Results from these studies will provide more information whether or not the BCG vaccine indeed protects against COVID-19.

BCG vaccination prevents severe forms of tuberculosis in children and diversion of local supplies may result in neonates not being vaccinated, resulting in an increase of disease and deaths from tuberculosis.

Researchers and journalists need to be responsible not to raise false hopes based on weak evidence.  In the absence of clear and robust evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19. WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis.

Countries with a TB vaccine seem to have fewer coronavirus deaths

A preliminary study finds a potential ally against COVID-19: the TB vaccine.

COVID-19 has spread to most of the world and continues to spread farther and farther. However, the impact of the disease can vary significantly from area to area. Much of this can be attributed to societal factors (such as average age, smoking rates, rate of underlying health issues) or to the performance of national health systems. But another factor, some researchers propose, has to do with vaccination — TB vaccination, to be exact.

The study published on medRxiv (a site for preliminary medical research) finds an intriguing correlation between countries that require people to get the Bacillus Calmette-Guerin (BCG) vaccine and those showing fewer numbers of confirmed cases and deaths from COVID-19.

Lead author Gonzalo Otazu, assistant professor at the New York Institute of Technology, says he was surprised by the relatively low number of cases in Japan — a country with an older population and which has not taken the strict quarantine measures imposed in many other parts of the world.

Japan has had a policy of universal BCG vaccination of infants against tuberculosis (TB) since 1951. Otazu and colleagues then inspected several other countries, assessing how the presence of a BCG vaccination correlates with COVID-19 severity.

According to their analysis, if a population is vaccinated against TB, it has better odds of faring better against the coronavirus.

“We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies,” the study authors explain.

‘It’s like the BCG vaccine creates bookmarks for the immune system to use later’, Otazy commented. The correlation was also observed in countries that introduced the vaccine later on (and in which the elderly population is unvaccinated and therefore more vulnerable).

“Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population.”

A “weird” vaccine

It’s not entirely surprising that a vaccine against one pathogen would offer partial protection against others. The BCG vaccine, in particular, interacts with the human body in a complex way which is not fully understood.

As far as approved vaccines go (and the BCG has been approved for almost a century), it’s one of the weirder ones. A 1994 systematic review found that BCG reduces the risk of getting TB by about 50%, with its efficacy varying significantly based on genetic factors. The BCG vaccine is also used against leprosy and some ulcerations. Remarkably, the vaccine has also become a key treatment against bladder cancer. According to one study, BCG is “the standard of care for patients with bladder cancer (NMIBC)” since 1977.

Notably, it’s not currently in use in many countries (notably the US and developed countries in Europe). It is, however, still mandatory in developed countries such as Japan and South Korea — both of which have had a remarkable track record against COVID-19.

Reactions from researchers on this preliminary study have been mixed. Some have criticized the correlation as speculative, which Otazu says he will address in a revised version of the study. The authors also emphasize that most data on confirmed cases from low-income countries were considered not reliable enough to make a strong judgment, and only reliable data was used.

However, it’s quite possible that the researchers are onto something here. It is probably not coincidental that several clinical trials are already investigating this avenue in the US, UK, Germany, and Denmark.

Perhaps the most intriguing of these clinical trials is carried out by Mihai Netea, an infectious-disease expert at Radboud University Medical Center in the Netherlands. Netea and his team enrolled 400 health workers in the trial, 200 of whom were administered the BCG vaccine, while the other 200 got a placebo. It will be 2 months or even more before the first results start coming in, but Netea is already working on a separate trial to study the effectiveness of the vaccine on people over 60.

It’s hard to say that exactly in what way the vaccine can protect against the coronavirus, particularly as TB is caused by bacteria, not a virus. It could be that the TB bacteria and the coronavirus use a similar attack strategy on the human body, which the vaccine offers some protection against.

For now, it’s hard to say just how effective the BCG vaccine is against COVID-19 — or even if it is effective at all. But it’s an interesting avenue worth researching.

More effective tuberculosis vaccine passes early trials in Africa

We may be closing in on a new, more effective vaccine for tuberculosis, according to a new paper published by members from GlaxoSmithKline’s Vaccine division.

Mycobacterium tuberculosis, the bacterium that causes tuberculosis.
Image credits NIAID / Flickr.

Tuberculosis is a curable, chronic lung disease. Despite this, it remains one of the deadliest infectious diseases of this day and age. It caused an estimated 1.5 million deaths worldwide last year alone. It’s also one of the world’s leading causes of death, particularly in developing countries, the team explains.

The vaccine we currently use against tuberculosis (TB), the Bacille-Calmette-Guerin (BCG) vaccine, was licensed for human use way back in 1921 and has only been proven effective for limited forms of the disease in children under five. It doesn’t protect against the most common form of the disease in adults and teens (pulmonary TB).

However, a GlaxoSmithKline trial in three African nations showed the vaccine to have a 50% effectiveness three years after it was given to TB carriers that had not developed the disease.

An exciting first step

“These results demonstrate that for the first time in almost a century, the global community potentially has a new tool to help provide protection against TB,” GSK Vaccines’ chief medical officer Thomas Breuer said in a statement released at a conference on lung health in Hyderabad, India.

The South African Tuberculosis Vaccine Initiative trials (carried out in Kenya, South Africa, and Zambia) involved over 3,000 adult participants, the authors report. The initiative’s director Mark Hatherill said a vaccine would be “the only way in the short-term to interrupt TB transmission and get control of the epidemic”. If successful, the vaccine could prevent millions of new TB cases and subsequent deaths all over the globe.

Around 15 possible vaccines are in various stages of development around the world says Ann Ginsberg of the International AIDS Vaccine Initiative, which has been taking part in the research, but that the one GlaxoSmithKline has been working on is the most “exciting”.

The results are not conclusive yet: they still have to face longer trials with more participants in other countries to make sure they’re broadly-applicable. This process could take several years.

It’s estimated that one in four people worldwide carry latent TB (they’re carriers but don’t get sick and can’t transmit the disease). Between 5% and 15% of them will develop active TB, and people with compromised or weakened immune systems are more vulnerable.

India, the country where the announcement was made public, accounts for a quarter of the world’s TB cases. Indian Prime Minister Narendra Modi has set an ambitious target of ending the epidemic by 2025.

The paper “Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis” has been published in the New England Journal of Medicine.

US FDA approves new treatment for drug-resistant TB

TB Medicine Pretomanid approved by the US FDA

The US Food and Drug Administration approved Pretomanid tablets as part of a three-drug combination regimen together with linezolid (Zyvox) and Johnson & Johnson’s bedaquiline (Sirturo) for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs.

TB is a bacterial infection that caused about 1.6 million deaths globally in 2017. It spreads through droplets when someone sick with TB sneezes or coughs. TB primarily attacks the lungs but can sometimes affect other organs.

Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are forms of tuberculosis that do not respond to first-line anti-TB drugs. XDR-TB, a more serious form of MDR-TB, is unresponsive even to the two most powerful anti-TB drugs – isoniazid and rifampicin – in addition to being resistant to certain second-line treatments.

Only a small fraction of the 10 million people infected by TB each year get drug-resistant TB, but very few of those who do survive it. According to the World Health Organization, in 2016, there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB.

Pretomanid is the generic name for the anti-bacterial drug formerly called PA-824.

The safety and efficacy of Pretomanid, taken orally in combination with bedaquiline and linezolid, was primarily demonstrated in a study of 109 patients with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs).

Of the 107 patients who were evaluated six months after the end of therapy, 95 (89%) were successes, which significantly exceeded the historical success rates for treatment of XDR- TB. Many TB patients are also infected with HIV. In the trial, the treatment worked as well for them as it did for other study participants. The drug regimen also appears to stop patients spreading the deadly bacterial infection after a few days’ treatment.

The most common adverse reactions observed in patients treated with Pretomanid in combination with bedaquiline and linezolid included damage to the nerves (peripheral neuropathy), acne, anemia, nausea, vomiting, headache, increased liver enzymes, indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhea.

TB Alliance developed Pretomanid, the first-ever US FDA-approved drug for XDR-TB

Pretomanid, was developed by the nonprofit group TB Alliance. “We can have a huge impact on the lives of people who are afflicted and also take a major step ultimately toward, really, the eradication of a disease like TB,” said Mel Spigelman, president and chief executive of TB Alliance.

Pretomanid is the first tuberculosis medication to be developed by a nonprofit organization. In addition to the United States, TB Alliance filed for approval of pretomanid in the European Union. TB Alliance hopes FDA’s approval will enable other countries, such as China, India and South Africa, to okay the drug and to make it available to their residents.

 “The threat of antimicrobial-resistant infections is a key challenge we face as a public health agency,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D.

“The bacterium that causes tuberculosis can develop resistance to the antibiotics used to treat it. Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs. That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections.”

Tuberculosis in Europe is in decline but every 2 minutes 1 person is still diagnosed with TB

Analysts from the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) recently reported that despite a decline in the incidence and mortality throughout Europe in people suffering from tuberculosis (TB), the trends among countries vary widely, and multidrug-resistant (MDR)-TB remains a major public health concern.

The joint WHO/ECDC report covers TB incidence and mortality for both the WHO European region, which includes 52 countries, and the 31-country European Union/European Economic Area (EU/EEA). In the WHO European Region, an estimated 275,000 new and relapse cases of TB occurred in 2017, for an average of 30 cases per 100,000 people. Eighty-seven percent of these patients (238,819) were notified. TB cases in the region represent nearly 3% of the global burden of the disease.

The absolute number of cases in the WHO European Region dropped by 15,000 from 2016, and the 4.7% average annual decline in incidence observed from 2008 through 2017 is significantly higher than the global rate of decline for TB incidence (1.8%).

TB mortality is also falling in the region. An estimated 24,000 TB deaths occurred in 2017 among HIV-negative patients in the WHO European Region, and the rate of 2.6 deaths per 100,000 people represents a 59% drop from 2008, when it was 6.3 per 100,000 people. The 10% annual decline over the past 5 years is notably higher than the 3.2% global decline observed from 2016 to 2017.

In the EU/EEA countries, 55,337 cases of TB were reported in 2017, for a notification rate of 10.7 per 100,000 people. The average annual decline in the notification rate was 4.5% from 2013 through 2017. The estimated number of TB deaths among HIV-negative patients in the EU/EEA was 4,000, down from an estimated 4,200 in 2016 and 6,700 in 2008. Although the decline in the notification rate is significant, the authors of the report point out that the 2030 target is a notification rate of 2.4 per 100,000.

Dr. Zsuzsanna Jakab, WHO

If the mean annual change in rate in low-incidence countries continues at that pace, they write, “calculations suggest the WHO target of TB elimination by 2050 in European low-incidence countries will not be met by approximately four-fifths of the countries currently in this group.”

Much of the gap in estimated incidence rates between the WHO European Region and the EU/EEA is driven by 18 high-prevalence non-EU/EEA countries (HPCs)—including Russia, Ukraine, Uzbekistan, Romania, Turkey, and Kazakhstan—that account for nearly 83% of the regional TB burden. The largest proportion of new and relapse TB cases comes from Russia (84,510, or 35.4%).

In addition, nine of the countries with the highest burden of rifampicin-resistant (RR)/MDR-TB burden—Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Ukraine, and Uzbekistan—are non-EU/EEA countries. The MDR percentage among new bacteriologically confirmed pulmonary TB cases in the non-EU/EEA countries rose from 16.8% in 2013 to 18.1% in 2017. Extensively drug-resistant (XDR)-TB is also a rising problem in WHO European Region countries. XDR-TB cases rose from 575 in 2013 to 5,591 in 2017.

“TB is preventable and curable; the time to take action is now to end TB by 2030,” Zsuzsanna Jakab, MD, WHO regional director for Europe, said in an ECDC press release. “If we don’t act rapidly and decisively, the drug-resistant forms of the disease will increase their hold on Europe.”

New hope for drug-resistant TB

Up until now, an MDR-TB diagnosis spelled the start of a long and cumbersome two-year treatment plan for patients. New WHO recommendations for the treatment of MDR-TB involve safer and more effective drugs with reduced chances of severe side effects and a new treatment regimen for increased effectiveness.

Timely diagnostic tests are vital

Proper and fast diagnosis of TB is essential. The sooner a patient is diagnosed, the faster their treatment can begin, easing suffering and preventing further disease transmission. To improve diagnoses and ensure appropriate treatment approaches, it is also important to have capacity at the country level to rapidly detect drug-resistant TB.

Overall, the situation in the European Region is improving slowly to end TB by 2030. To reach the SDG target on TB, new intersectoral approaches are required, current tools need to be used more effectively and a people-centered approach to care is essential.

HIV + tuberculosis, a deadly combination, affects over 1 million people

Some 1.2 million people worldwide are infected with both viruses. Now, researchers describe a new mechanism through which these viruses help each other, posing greater risks for patients.

Nanotubes linking two macrophages in humans infected with HIV-1 in a TB-associated micro-environment. Image credits: Shanti Souriant.

Throughout the centuries, tuberculosis has been present in many different countries and geographic areas. There is evidence that the pharaoh Akhenaten and his wife Nefertiti both died from tuberculosis, and anthropological studies at a site in Germany have shown that the disease affected people since the Neolithic. Tuberculosis became much more prevalent with the increase of urbanization, and at the end of the 19th century, it was one of the most urgent health problems. Thankfully, advances in treatment, vaccination, and overall sanitation drastically reduced the impact of tuberculosis — although the disease still remains highly prevalent, infecting 10 million people every year and killing 1.6 million in 2017.

Meanwhile, HIV spread dramatically during colonialist times in the 20th century. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, but with modern antiretroviral treatment, HIV rarely progresses to AIDS, and is regarded as a generally manageable condition in the developed world. It is still one of the most dangerous viruses in the world.

As if having one of the two viruses wasn’t bad enough, quite a lot of people have both — 1.2 million, according to an international team led by researchers at the CNRS and Inserm. The team also reports that in this case, the two viruses work together to do even greater damage than they would individually.

In the presence of tuberculosis, HIV-1 (the most widespread form of HIV) moves from one cell to another via nanotubes which form between macrophages, drastically increasing the percentage of infected cells.

Macrophages, a type of cell in the immune system that engulfs and digests unwanted pathogens, can serve as hosts for both tuberculosis and HIV-1 (the most widespread form of HIV). In the presence of tuberculosis, macrophages form tunnel-like nanotubes, which HIV can use to transfer from one cell to another, drastically increasing the percentage of infected cells.

This also produced a snowball effect: the more severe the TB, the more nanotubes were formed, which allowed HIV to infect more cells, generating more macrophages, more nanotubes, and so on.

But there is a silver lining to all this: the specific type of macrophage can be assessed through soluble markers in the blood, which means that diagnosis and treatment of patients suffering from both illnesses can be facilitated. Scientists were also able to use existing treatment to inhibit the formation of these macrophages, thus reducing viral transfer and HIV-1 production.

The study “Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages” has been published in Cell.

 

Mycobacterium tuberculosis Bacteria, the Cause of TB. Credit: Flickr, NIAID.

Tuberculosis could be eradicated by 2045 — if the world is willing to invest $2 bln./year

Mycobacterium tuberculosis Bacteria, the Cause of TB. Credit: Flickr, NIAID.

Mycobacterium tuberculosis Bacteria, the Cause of TB. Credit: Flickr, NIAID.

Tuberculosis is responsible for the deaths of 1.6 million people annually around the world, more than any other infectious disease. But tuberculosis (TB) can be cured with antibiotics and with enough effort, the disease could be contained so that it stops infecting communities. According to a new study performed at the University of Hawai’i, TB could be eradicated in less than three decades with effective treatment and prevention policy. The catch: it would require a cumulative investment of $2 billion per year to fund the effort.

Tuberculosis is very dangerous. It’s also curable

TB is caused by bacteria called Mycobacterium tuberculosis that attack the lungs. The bacteria spread through the air from person to person, making the disease highly contagious. It is also fatal if left untreated. Antibiotics are required to be taken for a relatively long time, typically for about 6 months.

The TB-causing bacteria mostly grows in the lungs and can cause symptoms such as:

  • A bad cough that lasts 3 weeks or longer
  • Pain in the chest
  • Coughing up blood or sputum (mucus from deep inside the lungs)

Other symptoms of TB disease may include:

  • Weakness or fatigue;
  • Weight loss;
  • No appetite;
  • Chills;
  • Fever;
  • Sweating at night.

Victoria Fan, an assistant professor of public health at the University of Hawai’i at Mānoa and one of the world’s foremost experts in tuberculosis, claims that the infectious disease could be eradicated with enough oversight.

She and colleagues published a new study in the journal Lancet Global Health outlying the steps world leaders need to take in order to reach this goal.

“If we direct global resources to curing people and preventing the spread of TB, we would save millions of lives and enormous amounts of money in the long run,” said Fan.

The best bang for our buck lies in early diagnosis. The more people with TB get properly diagnosed, the better the odds they can be saved while limiting exposure to yet-uninfected individuals. Currently, around 35% of cases of TB worldwide go undiagnosed or untreated.

At first, the costs for diagnosing and treating TB would increase substantially, but they are expected to drop dramatically once infection hotspots are contained.

And, although the financial effort to eradicate TB is huge, it’s well worth it. Even from an economic standpoint, each saved life means another contributing member to their respective economies. The researchers estimate that for every dollar spent in TB research and development in the US, the economy gains $16-$82.

“The goal of this Lancet Commission was to create a roadmap to a TB-free world,” Fan said. “The commission found that different countries will need different solutions. For example, in some countries, many people have TB that is resistant to certain antibiotics, so they need different plans than places where drug-resistance is less common.”

“Ridding the world of TB is a realistic goal,” Fan said. “Our report gives the health leaders of the world solid recommendations for action steps they can take to end this epidemic.”

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

New non-antibiotic treatment hijacks tuberculosis bacterium

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

Although the vaccine for tuberculosis (TB) was developed more than a century ago, infections are on the rise with 7.3 million diagnosed cases recorded worldwide in 2018 — this is up from 6.3 million two years prior. Once the first symptoms of the infectious disease set in, the patient needs to undergo a lengthy treatment with a powerful cocktail of antibiotics, which isn’t foolproof.

This is where a promising new treatment pathway identified by researchers at the University of Manchester may come in. The team found a way to treat TB in animals with a non-antibiotic drug.

The treatment works by targeting Mycobacterium tuberculosis’ defenses rather trying to destroy the bacteria itself.

Mycobacterium tuberculosis secretes molecules called Virulence Factors, which block the immune system’s response to the infection, making it extremely difficult to combat it. This is why people need strong antibiotics, often over 6 to 8 months. But even after the treatment is over, there’s a 20% risk that the infection will resurface.

Professor Lydia Tabernero, the project’s lead researcher, and colleagues targetted a specific Virulence Factor called MptpB, which, when blocked, allows white blood cells to destroy the bacteria more efficiently. In trials, monotherapy with an orally bioavailable MptpB inhibitor reduced infection burden in acute and chronic guinea pig models.

“The fact that the animal studies showed our compound, which doesn’t kill the bacteria directly, resulted in a significant reduction in the bacterial burden is remarkable,” Tabernero said in a statement.

Because MptpB isn’t found in humans, nor anything similar to it, the compounds used to block it are non-toxic to our cells.

What’s more, because the bacteria aren’t threatened directly, they are less likely to develop resistance against the treatment. Currently, the world is facing an antibiotic-resistance crisis that is threatening to undermine decades-worth of medical progress.

Scientists think that one in three people around the world is infected with TB, which kills 1.7 million annually. The disease is the most prevalent in Africa, India, China, but is on the rise in some western countries, particularly in the UK’s capital, London.

“TB is an amazingly difficult disease to treat so we feel this is a significant breakthrough,” said Tabernero.

”The next stage of our research is to optimise further the chemical compound, but we hope Clinical trials are up to four years away.”

The findings appeared in the Journal of Medicinal Chemistry.

Rats successfully sniff out tuberculosis in children

In a new study, researchers show that rats can be trained to detect tuberculosis (TB) in children — and they have a higher accuracy rate than the basic microscopy test.

Several species of African pouched rats have been trained to sniff out TB or landmines.

The study was inspired by anecdotal evidence that people suffering from TB have a very slight, distinctive odor. The disease is caused by a bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, spreading through the air when a person with TB coughs, sneezes, or talks — so it makes sense that the process might come with a particular scent.

Unfortunately, methods for detecting TB are far from perfect, especially in impoverished areas like sub-Saharan Africa and South-East Asia, which are often most at risk of contagion and where the disease is quite prevalent. In these areas, a cheap smear test is commonly used.

The test relies on analyzing a sample of sputum — the yucky mixture of saliva and mucus coughed up from the respiratory tract. The accuracy of the test greatly relies on the quality of sputum sample used. Quite often (and this is especially true for young children), patients are unable to produce a good enough sample and therefore their TB might go undetected.

Lead author Georgies Mgode of the Sokoine University of Agriculture in Tanzania comments:

“As a result, many children with TB are not bacteriologically confirmed or even diagnosed, which then has major implications for their possible successful treatment,” he explained. “There is a need for new diagnostic tests to better detect TB in children, especially in low and middle-income countries.”

Mgode and his colleagues have previously worked on training African giant pouched rats (Cricetomys ansorgei) to pick up the scent of molecules released by the TB-causing bacterium. Now, they’ve compared the rats’ detection work with existing diagnosis methods.

They obtained sputum samples from 982 children under the age of five who had already been tested using a microscopy test at clinics in the Tanzanian capital of Dar es Salaam. From the smear test, 34 of them were found to have TB, but the rats identified a further 57 cases which were confirmed by a more complex analysis method (the light emitting diode fluorescence microscope). In other words, rats successfully found 68% more cases of TB infection

“This intervention involving TB screening by trained rats and community based patient tracking of new TB patients missed by hospitals enables treatment initiation of up to 70%. This is a significant proportion given that these additional patients were considered TB negative in hospitals, hence were initially left untreated,” adds Mgode.

The news has already been passed to relevant clinics, and plans are underway for a broader detection campaign. The infected children in the study have been contacted for treatment.

The same type of rats has also been used to sniff out landmines.

Journal Reference: Mgode, G.F. et al. Pediatric tuberculosis detection using trained African giant pouched rats. DOI:10.1038/pr.2018.40

8 New Tools and Emerging Technologies For Tuberculosis

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

 

World TB Day is celebrated every year on March 24 to raise public awareness about the devastating health, social and economic consequences of tuberculosis (TB). World TB Day 2018 is exceptionally noteworthy because never in the history of TB has there been more attention and commitment to ending the infectious disease that kills 1.7 million people each year.

The animation below shows how TB spreads in the body and how the immune system fights it. It also illustrates the different ways the TB bacterium can develop into the disease; either through overwhelming the immune system (common in children) or by latent TB waking up and becoming active (typical for those with weak immune systems such as older people, those who are HIV positive, or have had organ transplants or chemotherapy).

Global progress depends on advances in TB diagnosis, prevention, and care in countries with high TB burden. In celebration of World TB day, here are eight new developments about tuberculosis drugs, vaccines, and diagnostics.

  1. TB is diagnosed using a skin test, or by culturing bacteria from a person’s sputum. Both methods can only be performed by trained microbiologists and may take several days to give results. Good news! Professor Alessandra Luchini, of George Mason University in Virginia, and her team developed a urine test that detects a specific sugar that coats the surface of TB bacteria and gives results in half a day.
  2. A team of chemists working in collaboration with doctors and public health researchers in South Africa has developed a new test that makes it easier to diagnose TB. The test developed by Professor Carolyn Bertozzi and the team at Stanford ChEM-H is called DMN-Tre and takes just a few steps and produces results in under an hour. They attached the sugar trehalose to a fluorescent dye that, once ingested, glows about 700 times brighter than before. When you see a very bright cell, it means live tuberculosis is present.
  3. The only licensed TB vaccine, BCG (Bacillus Calmette Guerin), was developed by Albert Calmette, a French physician and bacteriologist, and Camille Guérin, a veterinarian more than a century ago. However, a new study suggests that when given to adolescents who had been vaccinated as infants, a single dose of BCG could prevent a sustained TB infection by 45 percent.
  4. A newer live attenuated TB-vaccine ‘MTBVAC’ developed by Biofabri, Professor Carlos Martin and his team at the University of Zaragoza has finished Phase 1b trials carried out in healthy HIV unexposed newborn infants in South Africa, a country highly endemic for tuberculosis. MTBVAC was found to be well tolerated and induced a dose-dependent immune response that was distinct from the response induced by BCG. A subsequent Phase 2 trial in newborns to confirm its safety and to determine the final dose will go ahead in the next months.
  5. To create a better TB vaccine, a better understanding of the pathogenesis of TB is essential. A granuloma is an aggregate of cells and is the pathological hallmark of TB. To study how granulomas form, Professor Joanne Flynn and colleagues from the University of Pittsburgh use animal models, mainly using different macaques to watch how infection spreads in real-time. Flynn and her team developed an imaging modality called PET/CT, which uses fluorodeoxyglucose (FDG) as a probe, just like in cancer studies where they measure the level of inflammation or metabolic activity for each granuloma.
  6. The World Health Organization (WHO) has requested drug makers to submit an Expression of Interest (EoI) for Bedaquiline and Delaminid, two new-generation drugs, recommended for drug resistant-TB. Drugs passing the standards (or pre-qualified) will then be included in a list for procurement by the UN and other organisations.  This will ensure more manufacturers to supply quality medicines, which will make the market more competitive and prices more affordable.
  7. XDR-TB refers to strains of TB that are resistant to rifampicin and isoniazid and a fluoroquinolone and at least one of the three injectable TB drugs, capreomycin, kanamycin, and amikacin. The Nix-TB trial is the first TB clinical trial to test a new drug combination which has the possibility of being a shorter, all oral, and affordable treatment for XDR-TB. This combination does not require injections and has far fewer pills.
  8. Research conducted by Rockefeller scientists offers hope for a new and potent weapon against tuberculosis. Their work focuses on an antibiotic that kills MTB in the laboratory but is not suitable for clinical use. Fidaxomicin is uncommonly adept at killing tuberculosis cultivated in the lab. However, when taken orally, an antibiotic must be absorbed by the gut and eventually reach the lungs – but fidaxomicin is unable to do so. By understanding how fidaxomicin operates, the research by Rockefeller scientists could allow others to design new antibiotics that could be used to treat tuberculosis patients and might even work on other bugs.