On March 24, 141 years ago, German microbiologist Robert Koch announced to the world that he had discovered the cause of one of the oldest and deadliest diseases in history: tuberculosis. His discovery of the Mycobacterium tuberculosis bacillus opened the door to the search for a cure and a vaccine. The research into the therapies has paid off and is curable in most cases today, but access to the appropriate medication is necessary for this. Without it, 45% of patients die. However, the bacteria mutate and become resistant to the drugs, making it impossible to end the struggle to develop new drugs. Vaccination is still an open issue. There is only one that is more than a century old and has limited efficacy, although there are 16 new candidates in clinical trials, six of which are already in phase III when the drug’s safety and efficacy aspects have been thoroughly reviewed beforehand published. its marketing.
Despite the progress, the data urges further progress in both areas: in 2021 alone (latest available figures) there were 10.6 million new cases and 1.6 million people died as a result of the disease, making it the second deadliest infectious disease after Covid -19 power. 19, and the thirteenth leading cause of death in the world.
“It’s time to recognize it as a pandemic, address it as an emergency and put an end to it,” said Peter Sands, executive director of the Global Fund for HIV, Tuberculosis and Malaria, on the occasion of World Tuberculosis Day, which marks the anniversary of the discovery of Dr . cook thought. “We’ve managed to eliminate it as a public health threat in virtually every richest country in the world.” And yet we continue to cause millions of people to suffer and die from this preventable, treatable, and curable disease. In his opinion, the fight against this ailment is progressing “at a snail’s pace”. Incidence has decreased by 2% per year worldwide from 2000 to 2020. But with the outbreak of the Covid-19 pandemic this year, there has been a rebound for the first time in two decades, with 4.5% more new cases in 2021, according to the latest annual surveillance report, which the World Health Organization (WHO) publishes each year published in October.
In 2021, the highest percentage of new cases occurred in Southeast Asia at 46% of the total, followed by Africa (23%) and the Western Pacific (18%).
The slowness and setbacks in progress, which have become even more apparent with the speed at which Covid-19 has been tackled, have an explanation, experts say. “If a disease does not threaten the populations of rich countries, it is not even considered a pandemic. But tuberculosis meets all the requirements to be judged as such,” notes Sands. The numbers confirm his regret. In 2021, the highest percentage of new cases occurred in Southeast Asia at 46% of the total, followed by Africa (23%) and the Western Pacific (18%). In Europe, 2.2% were registered. “It is likely that tuberculosis will kill more people in low- and middle-income countries than Covid-19 by 2023,” predicts the expert. Which would once again position it as the deadliest infectious disease, at least in those countries.
Every year on this date, the WHO calls for a redoubled effort, more resources and an accelerated fight against tuberculosis. Also this anniversary he does it again under the motto “Yes, we can end TB!”. Since it published its latest study on the disease in October 2022, with data falling like a jug of cold water, some news have emerged that raise expectations of returning to the path of progress. One of the most encouraging was the start of vaccination in December 2022 in high-incidence sub-Saharan African countries – Senegal, South Africa and Madagascar – with a vaccine developed and manufactured in Spain (MTBVAC) to test its effectiveness. The project is in Phase III clinical trials, which will last five years, says Carlos Martín, principal investigator of the Vaccina Tuberculosis project at the University of Zaragoza. “We aim for greater than 50 percent protection, but our ideal would be to reach 80 percent based on the animal testing we’ve done,” he explains. He qualifies that what has been verified in the previous phases “has served to demonstrate its safety and immunogenicity [capacidad de un medicamento para generar respuestas inmunes]“. But it’s not the end of the road. We need to move on to the next stage: “Now we need to show that the more than 7,000 babies who are going to be vaccinated are safe; half with the current vaccine (BCG) and the other half with the MTBVAC”.
Without a vaccine, it’s clear that eradicating it will be virtually impossible
Carlos Martín, researcher at the University of Zaragoza
The target set in the UN Agenda 2030 to end tuberculosis completely by 2030 would require a 4-5% reduction in cases per year. “Without a vaccine, it’s clear that eradicating it will be virtually impossible,” says Martín. The only one that has existed for more than a century and is based on an attenuated strain of Mycobacterium bovis (from cows) offers very limited protection against the pulmonary forms of the disease responsible for its transmission. The one developed by the University of Zaragoza team is the only candidate of 16 in clinical trials based on a strain of Mycobacterium tuberculosis (human).
“What we do with the deletions contained in MTBVAC is to eliminate the virulence genes,” explains the technician. This means that without these genes, the bacillus is unable to attack its host and cause an infectious disease, but it does have an immunological response that protects the person from future incursions of the pathogen. “An attenuated strain of tuberculosis has never been approved in humans,” continues Martín, who hopes to get potential “Spanish financiers and philanthropists” excited when the European funds they’re insuring expire. “The idea is a single dose vaccine at birth that is cheap and can be widely distributed that is egalitarian. The condition of the University of Zaragoza is that it is affordable,” emphasizes the researcher.
In this spirit, the Galician biopharmaceutical company Biofabri and the Indian Bharat Biotech announced months ago an agreement to manufacture and distribute MTBVAC once it has the necessary approval in more than 70 countries in Southeast Asia and sub-Saharan Africa; including India, which bears the highest burden with 28% of all new infections in 2021.
barriers to entry and drug resistance
An MSF technician analyzes samples at the laboratory of the Drug-Resistant Tuberculosis Hospital in Kandahar, Afghanistan.Lynzy Billing (Lynzy Billing)
Experience with diagnostic methods and methods of treatment for tuberculosis shows that their existence is not a guarantee that they will reach their recipients. In addition to the underfunding of the fight against the disease in the countries that suffer the most – in 2020 it was 4.873 million euros, less than half (41%) of the global target – it happens that the impoverished population of not always the same There is a health center nearby where you can complete the six months of medication until you are cured. Irregular adherence to the regimen leads, among other things, to drug resistance. And these resistant strains spread from person to person.
There are also tests and drugs to detect and treat multidrug-resistant tuberculosis. But every third patient does not access it. Since December 2022, the WHO has recommended the BPaLM regimen, i.e. six months of bedaquiline (B), pretomanid (Pa), linezolid (L) and moxifloxacin (M). A shorter and less toxic therapy than the previous standard, up to 20 months and very painful. “The results of the PACTECAL study [sobre el régimen BEaLM] under the direction of MSF showed healing rates of almost 90%, much higher than the 52% achieved by the conventional regime. Likewise, it causes fewer side effects,” says Laura Moretó, an expert in the field of medical NGO. “But many countries still do not have access to some of the components, either due to their availability or their high cost, as in the case of bedaquiline, which still has a patent and is estimated to cost around 250 euros per treatment cycle.” Treatment”. At least one of these stumbling blocks was demolished in India this Thursday.
Successful patent challenge for bedaquiline to treat first-line drug-resistant form by two tuberculosis survivors, Nandita Venkatesan and Phumeza Tisile
“The 2019 patent challenge for bedaquiline by two tuberculosis survivors, Nandita Venkatesan and Phumeza Tisile, was successful,” MSF said in a statement. The Indian patent office has thus rejected an attempt by the pharmaceutical company Johnson & Johnson to extend its monopoly on the drug in the Asian country beyond the expiry of the primary patent next July. Generic manufacturers should be able to produce generic versions of the drug from 2023 and the US company should “not block the delivery of the cheapest to countries with a high tuberculosis burden,” the document says. According to Moretó, “The impact for the patient is clear: the opportunity to have a shorter oral treatment that is better tolerated, with a very high chance of recovery and a better quality of life after healing”.
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