Rates of new infections have been falling each year, but at a pitiful rate -- just 2% per year -- and experts in the field began to feel hopeless, drained and fed up by what should so easily be beaten.
That is until a special trial, beaming the number "54," woke them from resignation and gave the first signs of hope in years.
The number stood for a percentage -- 54%. It meant that a tuberculosis vaccine that crosses a coveted efficacy threshold may soon be possible -- and effective.
The vaccine, known as M72/AS01E
, has been developed by GlaxoSmithKline and is the first vaccine of many recent attempts to show more than 50% protection against people developing TB, as published in the New England Journal of Medicine
. Although the desire is 100% protection, experts believe more than half is enough efficacy to have a significant impact on new infections, possibly saving millions of lives and preventing 10s of millions of cases.
"I can't tell you the excitement," said Paula Fujiwara, scientific director at the International Union Against Tuberculosis and Lung Disease, also known as the Union.
"This is a hopeful place," she told CNN during the Union's 49th annual conference this week, in the Hague, Netherlands, where this and many other prevention options are being presented. "This could really help millions of people."
Many countries have had routine Bacillus Calmette-Guérin vaccinations, known as BCG, for tuberculosis for decades. Many adults received them as teens, for example in the UK, and now babies living in high-risk populations receive them as newborns. The vaccine is not generally recommended for use in the United States because of low risk of infection.
So why the desperation for a new vaccine? BCG has some deficiencies
, made evident in recent years -- it's only really beneficial to very young children and its protection doesn't continue into your adult years.
"BCG has little impact on TB in adolescents and adults," said Thomas Ottenhoff, professor of immunology at Leiden University in the Netherlands, during a session on vaccines at the conference Tuesday. "That's a problem because that's exactly when TB becomes highly contagious" and infections then spread in crowded living conditions, he said.
With a quarter of the world's population infected with a latent form of TB that could one day become active, when you come in contact with this airborne disease, you're going to want some protection.
"We need to prevent people getting infected in the first place," said Fujiwara. "Like the BCG intended."
Hundreds of developments in the field of TB are being presented at the conference this week, but two stand out as exciting options that could have an impact soon -- first and foremost the "game changer" vaccine.
Not yet protective for all
GSK's new vaccine candidate has one major caveat: It's only protective in people who are already infected with TB.
This prospect may not make much sense, but TB is a complex disease and protecting people who are already infected is just as important because people are able to carry the bacteria, Mycobacterium tuberculosis, for years -- possibly their entire lives -- without symptoms. Hence the billions latently infected worldwide, of which estimates show 10% will develop active TB.
While the infection is hidden, a person is not contagious, but a weakened immune system, for example by infections such as HIV, is all it takes to fire it up and activate the disease -- and enable people to spread it.
The new vaccine shows promise against this happening and its use on already-infected people proves its efficacy as a proof of concept, added Marie-Ange Demoitie, vaccine project leader for the development of vaccines against tuberculosis at GlaxoSmithKline.
The latest Phase 2b trial began in 2014 and took place in Kenya, South Africa and Zambia -- all high burden TB countries -- enrolling more than 3,500 participants, half of whom got the vaccine and the other half, a placebo. All participants were identified as being latently infected with TB bacteria, but had not developed the disease.
Two years later, a protection level of 54% was calculated and the vaccine shown to be safe to use.
"TB infected people can be protected," said Mark Hatherill, director of the South African Tuberculosis Vaccine Initiative. "But lots of questions remain unanswered."
The crucial question, Hatherill said, is whether uninfected people can get long-lasting protection.
In addition, a larger Phase 3 trial is now necessary among infected people and the vaccine's components need refining for even better efficacy, said Fujiwara, to further prove this vaccine's value and continue down the road to actual implementation in affected populations.
"You want to get it to the population," said Fujiwara.
Preventing infections in children
Another study presented at the conference Thursday showed remarkable success in preventing infections among children living with parents or adults who have active TB and using a shorter course of treatment than what is currently recommended under WHO guidelines.
"Children are at high risk in an adult-infected household," said Valérie Schwoebel, program manager for Francophone Africa at the Union, adding that very young children are at risk of more severe forms of the disease.
Current guidelines recommend at-risk children under the age of 5 take the anti-TB drug isoniazid as a prophylaxis every day for six months, but the latest WHO report states that just 23% of eligible children globally receive it. Fujiwara believes part of the problem is how long kids need to take it. "It's a long time," she said.
A new study tested out the benefits of a shorter treatment -- three months -- and got promising results.
Schwoebel's team recruited more almost 2,000 at-risk children in four countries: Burkina Faso, Cameroon, Central African Republic and Benin. In the first three countries, children were given two drugs, isoniazid and rifampicin, for three months, and the other country received the regular six month treatment.
Of participants who got either treatment regimen, just 5% were diagnosed with active TB over 18 months of follow-up. Both options were effective, but took half the time.
"This shows that preventing TB using a shorter regimen appears to be feasible," said Schwoebel, and as a result the intervention is already being scaled up and hopefully rolled out in these countries.
When it comes to adults, the greatest hope is a vaccine, but Fujiawara points out that efficacies around 54% mean they'll always have to be used in combination with other prevention measures, such as awareness and wearing masks where necessary.
But if this could all come together soon, millions of lives can be saved, said Fujiwara."TB is an ancient disease and it is curable," she said. "The fact that it hasn't been cured is a scandal."