The global tuberculosis (TB) crisis is fueled by several factors, including the alarming rise in drug resistance, reliance on obsolete, harsh drugs that often don’t work, lack of diagnostic tests that are practical for use in low-resource settings, and lackluster political commitment. Doctors Without Borders/Médecins Sans Frontières (MSF) is one of the main non-governmental providers of TB care worldwide, especially for people with drug-resistant TB, and helps lead global efforts to make newer, more effective treatments affordable and available to those who need them.
What causes TB?
TB is caused by bacteria that spreads by air when infected people cough or sneeze. It most often affects the lungs but can infect other parts of the body, including the bones and nervous system.
Most people who are exposed to TB never develop symptoms, although they can still harbor the infection in an inactive form. But if the immune system weakens, latent TB bacteria may become active and cause disease. About 10 percent of people with latent TB go on to develop active TB and become contagious at some point in their lives.
Who is most at risk?
Globally, TB crisis has grown dramatically since HIV became a widespread epidemic. That’s because people living with HIV/AIDS have weakened immune systems, which increases their risk of contracting and dying from TB—now the leading cause of death among people with HIV. People with other medical conditions that weaken immunity are also at a higher risk of TB infection and death. Children, the elderly, people from regions with high TB rates, and those living in close quarters like prisons, refugee camps, and crowded slums also face greater risk, as do members of households with someone who has active TB.
What are the symptoms of TB?
Many people infected with TB are asymptomatic but can develop an active infection if their immune system becomes weak. Symptoms, which may be mild at first, most often include a prolonged cough and fever. Weakness, chest pain, night sweats, weight loss, and shortness of breath are also common. While lungs are the most common site of infection, TB can affect almost any other body part or organ.
How is TB prevented?
Since TB is airborne it can be easily transmitted in crowded settings, from cramped households and workplaces to health care facilities. For example, people sharing a home with someone who has active TB are at increased risk of developing either a latent (asymptomatic) or an active infection. In these households, sleeping in separate rooms, wearing surgical masks, and using proper cough and respiratory hygiene can limit transmission. Children in these homes, especially those under five years old, are particularly vulnerable. Within health clinics, rapidly attending to patients with TB symptoms and starting treatment quickly for those with active infections lowers the chance they will pass it on to others. Proper ventilation systems within hospitals and the use of face masks that filter out particles in the air can also reduce TB spread.
In recent years the preventive use of TB medications for people at especially high risk of contracting TB—a treatment called Isoniazid Preventive Therapy, or IPT—is gaining ground, although many people who could benefit still do not receive it. It is most often given for defined periods of time (typically 6-36 months) to people living with HIV who do not have active TB, pregnant women in high-TB settings, household contact of TB patients, especially young children, and others with high exposure to TB.
Active Case Finding (ACF) is another preventive approach, based on screening high-risk people (such as household contacts or people with HIV) outside the clinic rather than waiting for them to seek care for their symptoms. ACF can also be used for population-based screening of broader vulnerable groups.
How is TB diagnosed?
The majority of people infected with TB have not been diagnosed, usually because tests are not available where they live or are not a routine part of primary care. Of the estimated 10 million new cases of TB in 2018, only 7 million cases were reported. Development of simpler, more accurate and cheaper diagnostic tools is, therefore, a critical need.
Until very recently, TB was most commonly diagnosed by examining patient sputum samples (phlegm coughed up from lungs) either under a microscope or by bacterial culture. But both methods require a laboratory and trained technical staff, making them ill-suited for many low-resource settings. And neither test is reliable in children, people with HIV, people with TB outside the lungs, or those infected with drug-resistant TB. In the case of culture, it can take as long as 8 weeks to get a result, which delays patients in starting treatment.
In 2010, a much faster, more accurate diagnostic test called GeneXpert MTB/RIF was introduced and is now used for most patients. It gives results within a few hours and can also distinguish between drug-sensitive and drug-resistant TB. While it represents a big improvement, it still requires a laboratory with stable electric power, trained technicians, and other supplies and infrastructure. And since it relies on sputum, it cannot diagnose TB in patients who cannot cough up sputum or who have TB outside the lungs.
In recent years, MSF and others have tested the usefulness of a urine-based test called TB LAM, which is rapid, inexpensive, and easy-to-perform without electricity or instruments. Due to its lower sensitivity (which means that it misses many positive diagnoses) TB LAM cannot replace other tests, but in combination with GenXpert MTB/RIF, it can help diagnose TB cases in people living with HIV and that would have otherwise gone undetected.
How is TB treated?
Uncomplicated, drug-sensitive TB is curable, but treatment takes at least six months and relies on a cocktail of the same harsh antibiotics that have been used for decades.
A growing number of people infected with multi-drug resistant TB (MDR-TB) are not cured by the two most powerful first-line antibiotics. As a result, most patients face between nine months and two years of treatment. Over this period they must swallow over 10,000 pills and endure 6-8 months of painful daily drug injections, often along with severe side effects that range from nausea and joint pain to psychosis and partial or total hearing loss. This should begin to improve, though, since new research has found a shorter regimen with these drugs that is no less effective even for MDR-TB. Patients with TB resistant even to the second-line drugs used for MDR-TB are said to have extremely drug-resistant TB (XDR-TB), which is even harder to cure.
In the last few years, much better outcomes have become possible using new, more effective, less harsh medicines. These improved treatments rely on three new drugs--the first new TB medicines in 50 years. For two of them (bedaquiline and delamanid) the best combinations with other TB drugs are still being evaluated, while the third drug, pretomanid, was developed as part of a ready-to-use regimen for treating XDR-TB.
Yet there are still big treatment challenges to solve. Access to the new drugs is extremely limited: fewer than 5 percent of patients who could benefit are receiving them, and they are not available in many countries most affected by TB. Also, most TB drugs are not made in formulations adapted for children, and effective treatment for TB/HIV patients is particularly challenging.
How MSF responds
We have been involved in TB care for over three decades, often working alongside national health authorities to diagnose and treat patients in contexts ranging from chronic conflict zones and refugee camps to urban slums, prisons, and remote areas. Our programs are designed to provide as many TB services as possible in outpatient community settings rather than in district hospitals. We also work to expand the range of available services by bringing newer, better diagnostic tools and treatments into more widespread use so more patients can access them. In 2019, we provided care for TB patients in 30 countries with a focus on very high TB-burden countries such as India, the Russian Federation, and South Africa, and on regions with very limited access to TB care, like in Somaliland.
Research and advocacy are also crucial to our strategy. Alongside operational research to improve how we deliver care, we have several clinical studies in progress to develop the best combinations of new and old drugs for drug-resistant TB, aimed at finding shorter, all-oral regimens. We also conduct policy research in high-burden countries to identify barriers that hinder the use of new tools and approaches recommended by the World Health Organization. This research helps drive our advocacy on reducing the costs of new tools and scaling up broad global access to improved treatment strategies, diagnostics, and models of care.
Decentralizing and innovating care
For most TB patients treatment is long and difficult, often involving harsh drugs, and debilitating side effects—especially for those with MDR-TB, who may also face long periods of hospitalization. These factors make it difficult for many people with TB to seek or stick with, treatment. In response, and working within each country’s national guidelines, MSF has introduced strategies to simplify treatment, make it more tolerable, and bring it closer to patients.
A key aspect of expanding access to TB care and helping patients complete their treatment is decentralization—treating patients in community-based clinics and no longer requiring hospitalization for those with MDR-TB, a shift ushered in by changes to World Health Organization recommendations in 2014. Since then, many countries have made this change, although some still lag behind. To help implement this shift, MSF supports many local health clinics in diagnosing, treating, and monitoring TB patients.
An important part of decentralizing care is task-shifting. For settings with too few physicians, this means training clinic nurses to give patients TB medications and monitoring their response over time. It also means training ‘expert patients’ to support, educate and counsel their fellow patients. Task-shifting allows us to care for many more people and to foster stronger links with local clinics, which makes it easier for people to continue their treatment.
One of MSF’s most successful community-based TB projects is in Eswatini (formerly called Swaziland), a tiny country in southern Africa but with some of the world’s highest rates of new TB infections and HIV prevalence. In 2008 MSF began treating TB (and HIV) patients in communities of Shiselweni, a remote, rural region. Five years later an evaluation found that this program had greatly increased the number of TB patients being diagnosed, successfully completing treatment, and reporting satisfaction with their care. Decentralization and innovation have also been critical to providing care for TB patients in Papua New Guinea, where mountainous terrain, dense forests, lack of roads and remote villages prevent many people from reaching treatment services. In response MSF teams have expanded outreach efforts, often traveling for hours by boat and road to visit health posts in small villages, or organizing transportation to help patients reach care.
Another strategy MSF uses to decentralize care is to offer home-based options for patients receiving treatment for MDR-TB. These build on Directly-Observed Therapy (DOT), where patients visit the clinic daily so a healthcare professional can watch them take their daily dose of medication—a widely-used approach to help patients with drug-sensitive TB adhere to complex regimens, and to help caretakers monitor their response. As an alternative to DOT, MSF now offers video-observed treatment to some MDR-TB patients who have difficulty reaching our clinics.
Caring for children living with TB
As challenging as it is to manage TB in adults, it is even harder in children, whose less robust immune systems make them especially vulnerable to developing TB. Diagnosis can be complicated since children often cannot cough up phlegm, which is used for most diagnostic tests. And many drugs that treat TB—especially MDR-TB—are not produced in pediatric doses, leaving children to take bitter-tasting pills cut into small pieces and crushed. Prolonged hospital stays can isolate children from their families, peers, and schooling. What’s more, children are often excluded from clinical trials that test shorter regimens and new medications, so the benefits of improved, more tolerable treatments take longer to reach them.
For these reasons, our TB programs work to improve TB care for children. One way is through partnerships with Ministries of Health, like that which established our pediatric TB program in Tajikistan. This program, which focuses on drug-resistant TB, uses specialized diagnostic methods such as using a nebulizer machine to help children produce sputum, and introduced treatments with new DR-TB medicines like bedaquiline and delamanid, and without injectable drugs. For children who cannot swallow tablets, the MSF pharmacist prepares medications in a syrup suspension, improving palatability of these medications and allowing for more exact dosages. The program employs teachers to provide basic schooling, runs a therapeutic playgroup, and holds group counseling sessions for hospitalized children to help them cope with the challenges of living with TB.
Treating TB and HIV under one roof
TB is the leading cause of death among people infected with HIV, whose weakened immune systems increasing their risk of TB and worsen its course. Ensuring that people with HIV are taking antiretroviral therapy (ART) as well as TB preventive therapy increases their protection against TB. For people with both HIV and TB, integrating treatment for both infections at a single clinic—a relatively recent development in many settings—makes it far easier and more likely they will receive the care they need. At MSF our integrated, decentralized model of care typically brings together diagnosis, treatment and patient support and counseling for patients with both HIV and TB. For example, in the Manzini region of Eswatini we supported the Ministry of Health to implement HIV/TB integrated care and adherence counseling sessions close to patient’s homes, leading to significant improvements in HIV and TB care services.
Developing better TB drugs through clinical trials
Only three new drugs have been developed in the past 50 years: bedaquiline, delamanid, and most recently pretomanid. While the first two are proving to be more effective than older drugs, including against highly drug-resistant TB, the research that led to their approval did not test the most effective combinations with existing drugs, ways to reduce or eliminate the harsher drugs, or to shorten treatment. (Pretomanid was developed as part of a regimen to treat XDR-TB.)
To this end, MSF is participating in two major clinical studies to find shorter, more effective, and less toxic treatments for MDR- and XDR-TB.
TB-PRACTECAL is aimed at developing treatments that can cure all forms of XDR-TB within six months, rather than the current nine- to twenty-month regimen. MSF ended enrollment in the study early (in March 2021) after the study’s independent Data Safety and Monitoring Board found that the trial’s new drug regimen was far superior to the current standard of care. These data will be shared with the World Health Organization and, once full results are available, submitted to a peer-reviewed medical journal. This finding has enormous potential to improve clinical care and patient quality of life, and, ultimately to save the lives of many more people living with XDR-TB.
EndTB is a partnership between MSF, Partners In Health, Interactive Research and Development and their partners. Together these groups conduct clinical studies that test the safety and effectiveness of new, short, all-oral regimens for MDR-TB compared to regimens with injectable drugs. endTB is using combinations of bedaquiline and delamanid with older drugs. These studies are still ongoing, but initial findings already show that the new regimens are more effective and less toxic than those with injections. This evidence underscores how urgent it is to make bedaquiline and delamanid accessible to all patients who need these drugs.
A fundamental step to effectively combat the TB epidemic is that affected countries adopt the World Health Organization’s (WHO) recommended best practices for TB diagnosis and care. Our Step Up for TB 2020 study—a collaboration between the MSF Access Campaign and the Stop TB Partnership—shows that too few high-burden countries have updated their national policies to reflect new WHO guidelines, leaving thousands of people more vulnerable to this curable disease. It also leaves a deadly diagnostic gap: an estimated 3 million people with TB go undiagnosed every year (WHO Global TB Report 2018 factsheet). 'Step Up for TB’ is part of a series of reports since 2014 that have helped countries identify barriers to adopting the newest WHO guidelines and measure progress over time, and have helped inform efforts of TB advocates.
Through the Access Campaign we also work to expand access to better TB drugs and less harsh, more tolerable drug regimens, by advocating for a wide range of reforms and for drug companies to lower the price of crucial new medications like bedaquiline.
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