Hey readers,
You probably don't think about tuberculosis much. Growing up, I only read about it in history books, where it was often referred to as consumption and where it shortened the lives of such famous people as the poet John Keats, the playwright Anton Chekhov, and all the Brontë siblings. It's a bacterial disease that lives mostly in the lungs, though if untreated it can spread throughout the body.
As recently as the turn of the 19th century, an estimated 7 million people a year died from tuberculosis. Even today, without modern medicine like antibiotics, it kills about half of people affected.
With access to modern medicine, though, tuberculosis is entirely treatable. But we haven't yet succeeded at consigning it to the history books. It still kills more than a million people a year, mostly in Southeast Asia, Africa, and the Western Pacific. In 2020, it took 1.5 million lives as the second deadliest infectious disease behind Covid-19, and, after years of general decline, during the past year tuberculosis deaths started rising.
What could we do to change that? There is a tuberculosis vaccine, which reduces susceptibility to an active case of the disease by about 60 percent. Relentless campaigns have ensured it's one of the most administered shots in the world, while the Directly Observed Therapy (DOT) protocol for drugs is a highly effective treatment for the sick.
But that doesn't mean our work is done; 1.5 million deaths is still way too many, and as long as tuberculosis circulates, it raises the chance of the disease developing multi-drug resistances that make it harder to treat with medication.
A better vaccine
One thing that would make a huge difference for the fight against tuberculosis would be a better infant vaccine — and there are some candidates in the works. Recently, I heard from 1Day Africa, the African division of the nonprofit 1DaySooner, which works toward developing vaccines faster and ensuring everyone in the world can access them, about efforts in Malawi to get a human challenge trial of a promising new TB vaccine underway.
The logic of human challenge trials goes like this: Normally, vaccines are tested by vaccinating lots of people, and then waiting until some of them naturally get exposed to the disease. But that can mean the trials last for years, with millions of people dying in the meantime. For some vaccines, then, it makes more sense to test directly: A few weeks after volunteers are vaccinated, they are exposed to the infectious disease and monitored to see if they get sick (and make sure they get the medical treatments needed to recover if they do).
Challenge trials have been used for diseases like malaria and cholera. But they aren't usually conducted for tuberculosis, partially because the long latency and long required course of treatment for the disease make such trials tricky. For years, though, tuberculosis researchers have been arguing that the human challenge model could significantly accelerate research and development on a better TB vaccine.
"The human challenge model could change the field of TB vaccine development as the malaria human challenge model did for malaria vaccines," one 2014 paper argued. A 2022 preprint attempted to estimate the scale of those benefits, and found that they're massive: "challenge models with even scant probabilities of expediting TB vaccine authorization have enormous expected humanitarian value, saving between 33,000 and 1,375,000 lives over the next ten years."
A Malawi-Liverpool collaboration
There's yet to be a tuberculosis human challenge trial, with a lot of institutional signoffs needed before it can go ahead. But Zacharia Kafuko, the director of 1Day Africa, told me there's finally been progress on changing that. It has come from the Malawi-Liverpool Wellcome Trust Clinical Research Programme (MLW), which is based in Blantyre, Malawi.
MLW is a world-class research hospital that hosts a lot of work I'm excited about, from malaria vaccines to schistosomiasis treatments to research on antibiotic resistance and drug-resistant disease. Every few years, the Royal College of London distributes a prize — endowed back in 1895 — to a leading tuberculosis researcher. The 2022 winner was Dr. Henry Mwandumba, interim director of MLW.
MLW has done challenge trials for other vaccines in Blantyre before, and Kafuko said that the local community in Blantyre is enthusiastic about taking part — and, if anything, annoyed that the approvals for this research are taking so long.
"The local community is very pleased to have this study done and some had actually expressed a wish to have had this study commence sooner and pioneered from Africa as opposed to Liverpool. The community where the study is proposed to take place like many places in Africa has a high TB burden and people feel this will help them and save lives," Kafuko said.
In a 2020 paper, researchers at MLW working on a human challenge trial for a pneumococcal vaccine conducted focus groups with researchers and local residents in Blantyre, and found that local residents were broadly in favor and excited about research happening near them instead of far away in Europe. "It's indeed right to conduct the research […] the drugs we have here were developed in Europe and maybe because of differences in climate and our bodies; those drugs don't work here," one village chief said.
Unfortunately, many of the medical devices used for the study are from the UK, where permission has been harder to secure and ethical reviews are likely to take a long time. The 1DayAfrica and MLW representatives I talked to sounded more than a bit frustrated about that — as I think they should. It's in Malawi that people are watching their loved ones die of tuberculosis. It's in Malawi that people have stepped forward to volunteer to help test a vaccine that could change that. It's in Malawi that doctors and nurses are ready to run this trial.
For a start, ethics review in the UK should be expedited in light of the enormous ethical costs — 1.5 million people dead every year! — of failing to address TB. If the team in Blantyre is ready to go, I think the UK should make sure to do its own review process in a way that does not end up delaying critical research their colleagues at MLW are ready to conduct.
And as a bigger-picture matter, I think that rich countries should think about the implications of setting the standards (through not sending medical equipment needed for research until our own ethics reviews are complete) by which people in other countries who directly face infectious diseases can organize to conduct critical scientific research to combat them.
I don't know what it's like to watch the people I love die of TB. So if the people who do know say they're ready to accelerate vaccine development with human challenge trials, I think our job is to send them all the supplies they need.
—Kelsey Piper
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