Tag Archives: TB

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.

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.

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.

Global Fund Crunch Threatens Millions of AIDS, TB, Malaria Patients

HYDERABAD(South India): The precious lives of millions of people suffering from  AIDs, Tuberculosis and Malaria, that take a heavy toll of life every year across the world, are at stake with the Geneva-based “Global Fund(GF)” financing several countries to fight these diseases, announcing stoppage of funds till 2014.

Bogged down by allegations of  swindling and mismanagement of funds,  and the  crunch, triggered by the worst debt crisis in donor countries of Europe and the USA forced the GF to take this extreme step, ringing alarm bells in the beneficiary nations including India.

The Global Fund to Fight AIDS, Tuberculosis and Malaria is an international financing institution that invests the world’s money to save lives. To date, it has committed US$ 22.4 billion in 150 countries to support large-scale prevention, treatment and care programs against the three diseases.

It was only a few days ago in Ghana that the Board of the Global Fund had adopted a 5-year plan to contribute substantially to international goals by saving 10 million lives and preventing 140-180 million new infections from AIDS, tuberculosis and malaria from during 2012-16.

Since its creation in 2002, the Global Fund has become the main financier of programs to fight AIDS, TB and malaria, with approved funding of US$ 22.4 billion for more than 600 programs in 150 countries. The Global Fund works in close collaboration with other bilateral and multilateral organizations to supplement existing efforts in dealing with the three diseases.

Lamenting the development, Mr.Manoj Pardeshi, National Coordinator, International Treatment Preparedness Coalition-India (ITPC-India) said the development had left a ‘ tremendous setback to the agenda of expanding AIDS treatment access for all those in need’.

”The Global Fund is one of the most significant institutions in a fight against an epidemic that claims three million lives a year, and in its ten years has played a critical role in strengthening health programmes in many countries. It has supported 3.2 million out of the 6.6 million people currently on antiretroviral (ARV) treatment for HIV,” he said.

These 3.2 million lives are now in jeopardy as funds dry up and existing treatment programs may have to shut their doors. People who would have been spared from death will now instead fall ill and die.

Ironically, such decisions are being made at a time when scientific evidence demonstrates that ARV treatment can both saves lives and prevent new infections. Rather than implementing ambitious plans to scale up the provision of treatment as outlined by U.S. Secretary of State Hilary Clinton in her address earlier this month, countries and communities will now need to discuss how best to manage a treatment scale-down, Mr.Manoj said.

The shortfall in funding for the Global Fund is $10 billion, an insignificant amount in comparison to the bank bailouts made by the US and European governments or even the bonuses set aside for Goldman Sachs executives this year.

Instead the Global Fund has put in place an emergency “transition mechanism” to safeguard only those countries that have current Global Fund grants and who will face program disruption between 1 January 2012 and 31 March 2014.

The restricted funding can only be used for essential prevention, treatment, and/or care services. However, such decisions will be devastating for organizations working in communities around the world.

Trends indicate that funding for HIV had already begun to fall flat by the end of the last decade. Last year the Global Fund failed to raise the minimum $13 billion that was needed to maintain its current programmes.

And of the overall $20 billion target, it raised roughly one-half, with $11.5 billion secured in pledges. To make matters worse, this year the Global Fund has been struggling with addressing the misuse of funds by recipients in a number of countries.

The lack of political and financial commitment to the AIDS response is deeply worrisome, and the millions of people living with and fighting against these deadly diseases will pay an enormous price.

Rather than building on the new evidence that AIDS treatment saves lives and prevents new infections and scaling up treatment programs to try to end this epidemic, donor governments are now implicitly supporting a policy of triage, determining who lives and who dies.

”Failure to invest in the fight against AIDS now simply means a return to the days of daily funerals and overflowing hospital wards. The virus doesn’t wait on the whims of donors,” he regretted.

The decision by donors will entrench the epidemic once again around the world, drastically increasing the costs of containing it when the world’s leaders once again wake up to the crisis around them.

The AIDS epidemic is far from over, but with a sustained commitment to comprehensive treatment, prevention and care services, it is still possible in our lifetime to create an AIDS-Free Generation.//EOM//