Which infectious disease has taken the most lives worldwide? COVID-19 is fresh in our memories, but you may also think of malaria, HIV, cholera, and Ebola as terrifying contagious diseases. The number of deaths from infectious diseases fluctuates over time, and indeed if you look at 2021, when COVID-19 was rampant, it was the deadliest infectious disease that year. However, over a longer horizon, it is believed that no infectious disease has claimed more lives than tuberculosis. Although deaths from tuberculosis are on the decline, more than 1 million people still lose their lives to it every year worldwide. Most of these deaths are concentrated in Asia and Africa.
In a report released in 2024, the World Health Organization (WHO) identified tuberculosis as the infectious disease that killed the most people in 2023. In that single year, an estimated 10.8 million people fell ill with TB, about 8.2 million were diagnosed, and 1.25 million died from the disease.
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The bacteria can affect various parts of the body such as the kidneys, brain, spine, and skin, but most often it infects the lungs, causing pulmonary tuberculosis. Symptoms include fever, cough, blood in sputum, and chest pain; without treatment, the disease can become severe and fatal. Today, however, there are effective treatments and a preventive vaccine for TB, and in high-income countries it is often regarded as a disease of the past. Nevertheless, TB continues to claim many lives. Why does TB, despite having treatments and a vaccine, remain a deadly disease? To address this question, we introduce two articles on tuberculosis from the news outlet The Conversation.
The first, published on October 31, 2024, is by Tom Nyirenda: “TB in Africa: global report shows successes, but Nigeria and DRC remain important hotspots.” The second, published on October 30, 2023, is by Charles Shey Wiysonge: “TB vaccine: WHO expert explains why it’s taken 100 years for a scientific breakthrough, and why it’s such a big deal.”
Through these two articles, let’s examine why TB continues to take so many lives despite available treatments and vaccines, and what the future may hold.
Stained Mycobacterium tuberculosis observed under an electron microscope (Photo: NIAID / Flickr [CC BY 2.0])
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TB in Africa: The global report shows successes, but Nigeria and the Democratic Republic of the Congo remain in a serious situation
《Translated article from The Conversation, by Tom Nyirenda ( Tom Nyirenda ) (※1)》
The WHO’s “Global Tuberculosis Report 2024” lays out a stark reality. Major challenges remain in the fight against TB, the pathogen that caused the most deaths worldwide in 2023. These include persistent poverty in heavily affected countries, rising infection rates among vulnerable populations, the difficulty of finding and treating everyone with TB before symptoms develop, and funding shortfalls.
The WHO report gauges the situation in two ways: TB-related deaths and the number of people who developed TB. This disease, which each year emerges in more than 10 million people already infected with the bacterium and claims around 1.5 million lives, will require a prolonged fight to eliminate—despite being both preventable and treatable.
There is good news, too. Several African countries have made substantial progress in reducing TB incidence and TB-related deaths.
Global health expert Tom Nyirenda assesses the report’s key findings and messages.
Poverty reduction can defeat TB
In 2023, an estimated 10.8 million people developed TB worldwide. The breakdown is 6.0 million men, 3.6 million women, and 1.3 million children. This is slightly higher than the 10.6 million recorded in 2022.
TB can be overcome because we have good diagnostics and effective treatments for the most common forms of the disease. But global financing—vital to the fight—still falls short of what is needed to curb TB. Of the funds pledged by global partners for TB prevention, diagnosis, and treatment services, only 26% has materialized so far.
Excellent diagnostic tools and treatments are not panaceas. About 87% of people with TB come from the 30 low-income countries most heavily affected by the disease. Slow or stagnant economic growth among affected populations remains one of the world’s greatest ongoing challenges.
A hospital in Somalia with a dedicated TB ward rendered dysfunctional by shortages of supplies and beds (Photo: UNICEF Ethiopia / Flickr [CC BY-NC-ND 2.0])
TB-related deaths
On the positive side, there has been progress in reducing TB-related deaths in the African region. Since 2015, TB-related deaths on the continent have fallen by 42%—the largest decline among the six regions. The European region follows with a 38% decline over the same period.
Regarding TB incidence, the WHO African and European regions have made the most progress, with reductions of 24% and 27% respectively.
One major reason for Africa’s success is improved treatment for people with HIV, as TB is one of the most common opportunistic infections among those living with HIV. (Opportunistic infections occur more frequently and are more severe in people with weakened immune systems.)
Before antiretroviral therapy transformed HIV care, TB-HIV coinfection rates in Africa were the highest in the world. Mortality was high among coinfected patients.
At one time, in several parts of sub-Saharan Africa, the proportion of TB patients who were also infected with HIV was estimated to be as high as 90%.
Treating coinfected patients with antiretroviral therapy has contributed greatly to the decline in TB cases and deaths across the African continent.
Some countries are strengthening TB screening among groups at higher risk, including children and people living in crowded settings such as prisoners and displaced people.
Participants in World Tuberculosis Day activities in South Africa on March 24, 2021 (Photo: GovernmentZA / Flickr [CC BY-ND 2.0])
A mixed picture in incidence
Success across the African region varies by country.
For example, Nigeria and the Democratic Republic of the Congo are two of the eight countries that together accounted for about two-thirds of the people estimated to have developed TB worldwide in 2023. Of the world’s new cases, Nigeria accounted for 4.6%, and the DRC for 3.1%.
It is worth noting that both countries have high levels of poverty, vast territories and large populations, and health services that are limited relative to the scale of the infectious disease challenges they face.
An increase in reported cases is not always bad news; it can reflect improved case finding and advances in diagnostics. However, vigilance must not wane if we are to stay on track toward the global targets (※2) set at the UN high-level meeting.
Barriers to accessing treatment
Families of TB patients often face reduced income along with costs for medications, special foods for TB patients, and transportation to clinics.
Such expenses can sometimes lead TB patients to refuse treatment.
According to the WHO’s global report, in many African countries families are estimated to face “catastrophic total costs” as a result of a household member having TB. This refers to situations where direct and indirect costs exceed 20% of a household’s annual income. Countries include Niger, Ghana, Burkina Faso, Tanzania, and South Africa, among others.
Collecting fingerprints needed to confirm clinic attendance for preventing drug resistance during TB treatment in India (Photo: DIVatUSAID / Flickr [CC BY-NC-ND 2.0])
The road to vaccine development
The Bacille Calmette–Guérin (BCG) vaccine, the only vaccine against TB, has been in use for over 100 years. It is widely effective in children under 5, but less so in older age groups, and it cannot be used in people with certain medical conditions.
Vaccine development takes a long time and is expensive. To date, only about one-fifth of the needed research funding has been raised.
There is encouraging news, however. Of all infectious diseases, TB likely has the most vaccine candidates in development—17 in total. There are six adult vaccine candidates in Phase III trials, which could become available within the next 5 years.
To beat this disease, we need an effective primary preventive TB vaccine; a recurrence-preventing vaccine for those with a history of TB; or a therapeutic vaccine for people already infected with the bacterium but not yet ill.
Future threats
Climate change will affect the stable food supply and nutritional status that are essential for recovery from TB. This could drive further spread and even trigger pandemics of TB.
Human conflict, migration, and displacement are other global threats that hinder TB control and treatment.
A response to drug-resistant TB is also urgently needed.
Amid such threats, multiple sectors are increasingly collaborating to share scarce resources and have meaningful impact. The rapid development of COVID-19 vaccines during the pandemic and global lockdowns shows that such cooperation is possible in both good times and bad.
What needs to be done?
Without government support, we cannot win the fight against TB. National and community contexts differ. Therefore, to introduce policies that reduce the economic burden of TB on communities, it is essential in every setting to conduct context-specific economic studies. The information obtained will underpin policies and actions. Above all, governments must lead and mobilize funds appropriately.
South African Deputy President at the time, David Dabede Mabuza, promoting TB prevention campaigns (Photo: GovernmentZA / Flickr [CC BY-ND 2.0])
TB vaccine: A WHO expert explains why a scientific breakthrough took 100 years, and why it matters
《Translated article from The Conversation, by Charles Shey Wiysonge ( Charles Shey Wiysonge ) (※3)》
The BCG vaccine for TB has been used for 100 years. The BCG vaccine is generally effective in children under 5, but less so in older age groups, and it cannot be used in people with certain medical conditions. Today, we are closer to finding vaccines that could replace or complement BCG. Charles Shey Wiysonge, WHO Regional Advisor for Immunization, discusses the latest developments in the fight against one of the world’s most serious diseases.
Why has it taken so long?
New TB vaccines are not yet complete. But for the first time, several candidates have advanced to later stages of clinical development.
Vaccine development typically takes decades, moving step by step through each phase. Experimental vaccine candidates are created in the lab, tested in animals, and then progressively move into larger clinical trials in humans.
Clinical trials are studies that test medical interventions, such as vaccines, in people, and proceed in sequential phases from Phase 1 to Phase 3. Once a vaccine reaches these stages, it is said to be in clinical development.
Phase 1 clinical trials are the first studies in humans, evaluating whether a candidate vaccine is safe in a small group (usually fewer than 100) of healthy individuals.
Phase 2 trials usually involve hundreds of participants and assess whether the candidate vaccine elicits an immune response.
Phase 3 trials involve thousands of participants to evaluate vaccine efficacy and safety. Phase 3 TB vaccine trials are currently underway in Gabon, Kenya, Russia, South Africa, Tanzania, and Uganda.
Even if it takes another 3 years before new TB vaccines receive broad regulatory approval, the scientific community can do much now to prepare for rapid rollout once they are available, and to inform the public so that the new vaccines are accepted.
Developing TB vaccines is very difficult. The TB pathogen is complex and adept at evading the human immune system. We still do not fully understand how best to target the bacterium or which immune responses are needed to enhance protection. However, several promising approaches are underway, and encouraging data are emerging from clinical trials that provide important clues.
A man receives a vaccine at a TB hospital in Dhaka, the capital of Bangladesh (Photo: en:United States Agency for International Development / Wikimedia commons [public domain])
Why do we need new TB vaccines?
TB is a global public health emergency. Around 2 billion people are currently infected with the TB bacterium. Of these, 5% to 10% develop disease and can transmit TB.
In 2021, about 10.6 million people fell ill with TB and 1.6 million died. New tools—especially improved vaccines—are urgently needed to fight TB.
The BCG vaccine has saved tens of millions of lives. It is effective in children under 5 and helps prevent death and severe disease from TB.
The vaccine’s protective effect against pulmonary TB (TB that causes symptoms in the lungs) in adolescents and adults varies. Since transmission is driven mainly by pulmonary TB, new and improved vaccines that effectively prevent pulmonary TB in adolescents and adults are essential to curb TB and reduce spread to everyone, including newborns.
TB is the leading cause of death among people with HIV. Those with HIV are 20 times more likely to develop TB than those without HIV. For safety reasons, the current BCG vaccine is not recommended for people living with HIV. While BCG is safe in immunocompetent infants (whose immune systems function normally), severe adverse events can occur after BCG vaccination in infants infected with HIV.
These adverse events, though rare, include a life-threatening condition known as disseminated BCG disease. New TB vaccine candidates are being developed and are being evaluated for potential clinical benefit in people with HIV.
How effective is the BCG vaccine?
The BCG vaccine is given at birth or soon after to more than 100 million children each year worldwide. Its effectiveness varies depending on several factors, including local TB epidemiology, the strain of BCG used, and the age at which BCG is administered.
Several studies show that BCG’s protection wanes as children approach adolescence. People may become infected with TB without noticing it.
The multiple puncture device used in Japan for BCG vaccination (Photo: Y tambe / Wikimedia commons [CC BY-SA 3.0])
What will happen to the BCG vaccine?
Unless compelling data demonstrate the safety and efficacy of alternatives, the BCG vaccine is unlikely to be replaced by other TB vaccines. Most vaccines currently in clinical trials are being tested in adolescents and adults. To replace BCG, a vaccine would need to prove safety and efficacy in newborns.
In addition, BCG vaccination appears to have non-specific beneficial effects on all-cause mortality, reducing child deaths beyond what can be explained by TB prevention alone. Therefore, it is very likely that BCG will continue to be used.
The significance of new vaccines in the fight against TB
The significance of new vaccines depends on what clinical trial data show. Above all, any new vaccine must be safe and provide clear clinical benefits to people at risk. We hope that the TB vaccine candidates in development will reduce TB infection, disease, and transmission, and become part of a useful combination of tools in the fight against TB.
※1 This article is a translation of The Conversation piece by Tom Nyirenda ( Tom Nyirenda ): “TB in Africa: global report shows successes, but Nigeria and DRC remain important hotspots.” We would like to thank The Conversation and the author, Tom Nyirenda, for providing the article.
※2 The global targets mentioned here refer to goals set at the 2023 UN High-Level Meeting on TB, to be achieved by 2027. These include not only treatment, prevention, and diagnosis, but also investments for implementation and further research.
※3 This article is a translation of a The Conversation piece by Charles Shey Wiysonge ( Charles Shey Wiysonge ): “TB vaccine: WHO expert explains why it’s taken 100 years for a scientific breakthrough, and why it’s such a big deal.” We would like to thank The Conversation and the author, Charles Shey Wiysonge, for providing the article.
Writer: Tom Nyirenda, Charles Shey Wiysonge
Translator: Seita Morimoto
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