WHO Global Tuberculosis Report 2018

Tuberculosis (TB) is one of the top 10 causes of death worldwide, and the leading cause of death from a single infectious agent. In 2017, an estimated 10 million people fell ill with TB, and 1.6 million died from the disease. The World Health Organization (WHO) is the global leader in providing guidance and support for TB prevention, diagnosis, treatment and care.

The WHO Global Tuberculosis Report is an annual publication that provides a comprehensive and up-to-date assessment of the TB epidemic and progress in the response at global, regional and country levels. The report also includes an overview of the latest innovations and research developments in TB diagnostics, drugs and vaccines.

The 2018 edition of the global TB report was released on 18 September 2018, in the lead up to the first-ever UN High Level Meeting on TB on 26 September 2018. The report presents data from 194 countries and territories that reported to WHO in 2018, covering 99% of the world`s population. The report highlights the achievements and challenges in the global fight against TB, and calls for urgent action to accelerate progress towards ending TB by 2030.

The full report and executive summary of the WHO Global Tuberculosis Report 2018 are available for download from the WHO website. The full report is a comprehensive document that provides detailed information on the global and regional burden of TB, the progress and challenges in TB prevention, diagnosis and treatment, the financing and implementation of TB programmes, and the research and development of new tools and strategies to combat TB. The executive summary is a shorter document that highlights the main findings and messages of the report. Both documents are in PDF format and can be accessed by clicking on the links below:

The report was first posted on 18 September 2018, in the lead up to the first-ever UN High Level Meeting on TB on 26 September 2018. The data in this report are updated annually. Please note that direct comparisons between estimates of TB disease burden in the latest report and previous reports are not appropriate. The most recent time-series of estimates are published in the 2018 global TB report. Minor updates were made to the report as follows:

• 21 September 2018: corrections made in Table 3.6 and Figure 6.2.2
• 9 October 2018: Annex 3 and Annex 4 were added
• 11 October 2018: a minor update to figure 3.25
• 30 October 2018: a minor update to box 4.3.

The report is also accompanied by a set of online annexes that provide additional data and information on various aspects of TB. These annexes can be accessed from the WHO website or by clicking on the link below:

Tuberculosis (TB) is an infectious disease that mainly affects the lungs, but can also involve other parts of the body. It is caused by a type of bacteria called Mycobacterium tuberculosis (M. tuberculosis). TB is one of the top 10 causes of death worldwide, and the leading cause of death from a single infectious agent.

TB is transmitted through the air when a person with active pulmonary TB coughs, sneezes, or speaks, and releases droplets containing the bacteria. People who breathe in these droplets can become infected. However, not everyone who is infected with M. tuberculosis will develop TB disease. Only about 5-10% of people with latent TB infection (when the bacteria are dormant in the body) will progress to active TB disease in their lifetime. The risk of developing TB disease is higher for people with weakened immune systems, such as those living with HIV, malnutrition, diabetes, smoking, or alcohol use.

According to the WHO Global Tuberculosis Report 2018, there were an estimated 10 million new cases of TB disease in 2017, of which 5.8 million were men, 3.2 million were women, and 1 million were children. About 9% of the new cases were people living with HIV. The six countries that accounted for 60% of the global total were India, China, Indonesia, the Philippines, Pakistan, and Nigeria. The report also estimated that there were 1.6 million deaths from TB in 2017, including 300 000 among people living with HIV.

TB can be prevented and cured with effective diagnosis and treatment. However, many people with TB remain undiagnosed or untreated, and some forms of TB are resistant to the standard drugs. These challenges pose a serious threat to global health security and require urgent action from all stakeholders.

To confirm the diagnosis of TB disease, it is necessary to identify the presence of the bacteria that cause TB, Mycobacterium tuberculosis, in the patient`s body fluids or tissues. There are different types of tests that can be used for this purpose, depending on the availability of laboratory facilities, the type and location of TB disease, and the urgency of the diagnosis.

One of the most widely used tests for TB disease is the rapid molecular test, which can detect the DNA of M. tuberculosis in a sample of sputum (the mucus that is coughed up from the lungs) or other body fluids. The test can provide results within 2 hours, and can also indicate if the bacteria are resistant to rifampicin, one of the main anti-TB drugs. The rapid molecular test that is currently recommended by WHO is the Xpert® MTB/RIF assay (Cepheid, USA), which has been shown to have much better accuracy than sputum smear microscopy, a traditional technique that requires examining sputum samples under a microscope. The Xpert® MTB/RIF assay was initially recommended by WHO in 2010 for diagnosis of pulmonary TB in adults, and since 2013 it has also been recommended for use in children and to diagnose specific forms of extrapulmonary TB (TB that affects other organs besides the lungs).

Another type of test for TB disease is sputum smear microscopy, which was developed more than 100 years ago and is still widely used in many low-resource settings. This technique requires examining sputum samples under a microscope to determine the presence of acid-fast bacilli (AFB), which are a group of bacteria that include M. tuberculosis. However, this test has several limitations: it cannot distinguish between different types of AFB, it cannot detect drug resistance, it has low sensitivity (especially in children and people with HIV), and it requires multiple samples and visits to the laboratory.

A more sensitive and specific type of test for TB disease is culture-based methods, which involve growing M. tuberculosis from a sample of sputum or other body fluids in a special medium. This allows for confirmation of the diagnosis, identification of the species and strain of the bacteria, and testing for drug susceptibility. However, culture-based methods require more developed laboratory capacity and can take up to 12 weeks to provide results.

Globally, use of rapid molecular tests is increasing, and many countries are phasing out the use of smear microscopy for diagnostic purposes (although microscopy and culture remain necessary for treatment monitoring). There are also tests for TB that is resistant to first-line and second-line anti-TB drugs. They include rapid line probe assays (LPAs) that test for resistance to rifampicin and isoniazid (referred to as first-line LPAs); a rapid LPA that tests for resistance to fluoroquinolones and injectable anti-TB drugs (referred to as a second-line LPA); and sequencing technologies. First-line LPAs were first recommended by WHO in 2008; the second-line LPA was first recommended in May 2016. Culture-based methods currently remain the reference standard for drug susceptibility testing.

One of the challenges in diagnosing TB is that the conventional methods of testing for the presence of bacteria in sputum samples are slow, insensitive and require well-equipped laboratories. Sputum smear microscopy, which was developed more than 100 years ago, can only detect about half of the cases of pulmonary TB, and has even lower accuracy in children and people living with HIV. Culture-based methods, which are considered the gold standard for diagnosis, can take up to 12 weeks to provide results.

To overcome these limitations, WHO recommends the use of rapid molecular tests that can detect TB and drug resistance within hours. The most widely used rapid test is the Xpert® MTB/RIF assay (Cepheid, USA), which simultaneously tests for TB and resistance to rifampicin, the most effective first-line anti-TB drug. The test has much better accuracy than sputum smear microscopy, and can also diagnose specific forms of extrapulmonary TB. Since its introduction in 2010, Xpert MTB/RIF has been adopted by 130 countries and more than 23 million tests have been procured through concessional pricing mechanisms.

Other rapid molecular tests include line probe assays (LPAs) that can test for resistance to first-line and second-line anti-TB drugs. These tests are also endorsed by WHO and are useful for confirming drug resistance in patients who have positive results from Xpert MTB/RIF or culture-based methods.

Globally, the use of rapid molecular tests is increasing, and many countries are phasing out the use of smear microscopy for diagnostic purposes. However, microscopy and culture remain necessary for treatment monitoring and quality assurance. WHO also recommends the use of sequencing technologies for drug susceptibility testing, as they can provide comprehensive information on the genetic mutations that confer resistance to anti-TB drugs.

The availability and accessibility of rapid molecular tests have improved the diagnosis and treatment of TB and drug-resistant TB, especially in high-burden settings. However, there are still gaps in coverage, quality and affordability of these tests. WHO estimates that only 39% of people with TB were tested with a WHO-recommended rapid diagnostic test in 2017. Moreover, there is a need for further research and development of new diagnostic tools that can be used at the point-of-care, especially for children and people living with HIV.

Drug-resistant TB (DR-TB) is a form of TB that does not respond to the standard treatment with first-line anti-TB drugs. DR-TB poses a serious threat to global TB control, as it is more difficult and costly to treat, and has worse outcomes than drug-susceptible TB. According to the WHO Global Tuberculosis Report 2018, there were an estimated 558 000 new cases of DR-TB in 2017, of which 82% had multidrug-resistant TB (MDR-TB), defined as resistance to isoniazid and rifampicin, the two most effective first-line drugs. Only about one in four people with DR-TB were diagnosed and enrolled in treatment in 2017, and only about half of those who started treatment were successfully cured.

Early and accurate diagnosis of DR-TB is essential for ensuring appropriate treatment and preventing further transmission of the disease. WHO recommends the use of rapid molecular tests that can detect TB and resistance to rifampicin (and in some cases also to isoniazid) within hours. The Xpert® MTB/RIF assay (Cepheid, USA) is the most widely used rapid molecular test for TB diagnosis. It can simultaneously detect TB and resistance to rifampicin in sputum or other specimens, with high accuracy and minimal laboratory requirements. WHO first endorsed this test in 2010, and since then it has been implemented in 130 countries. In 2017, about 10 million Xpert tests were procured globally, of which about 1.3 million detected rifampicin resistance.

Another type of rapid molecular test for DR-TB is the line probe assay (LPA), which can detect resistance to multiple drugs on a strip of nitrocellulose paper. WHO recommends two types of LPAs: a first-line LPA that can detect resistance to isoniazid and rifampicin, and a second-line LPA that can detect resistance to fluoroquinolones and injectable second-line drugs. These tests can provide results within one or two days, but require more laboratory infrastructure and biosafety measures than Xpert. WHO first endorsed the first-line LPA in 2008, and the second-line LPA in 2016. In 2017, about 1 million first-line LPAs and about 200 000 second-line LPAs were procured globally.

The reference standard for DR-TB diagnosis is culture-based drug susceptibility testing (DST), which involves growing the bacteria in the presence of different drugs and observing their growth patterns. This method can test for resistance to any anti-TB drug, but it is slow (taking up to 12 weeks), complex and prone to contamination. WHO recommends that culture-based DST should be performed at least once for all patients with DR-TB, preferably at the start of treatment, to guide the choice of drugs and monitor treatment response.

In addition to these conventional tests, new technologies are emerging that can potentially improve the diagnosis of DR-TB. One such technology is sequencing, which involves analysing the genetic code of the bacteria and identifying mutations that are associated with resistance to different drugs. Sequencing can provide comprehensive information on the resistance profile of a TB isolate, as well as its lineage and transmission dynamics. However, sequencing requires sophisticated equipment and bioinformatics capacity, and its interpretation is not always straightforward due to the complexity and diversity of TB genetics. WHO has issued interim guidance on the use of sequencing for DR-TB diagnosis in 2018, and is currently developing a consolidated guideline on molecular tests for TB.

TB is a deadly disease that can kill up to 70% of people who have sputum smear-positive pulmonary TB within 10 years of diagnosis, if left untreated. Even people who have culture-positive (but smear-negative) pulmonary TB have a 20% chance of dying without treatment. These estimates are based on studies of the natural history of TB disease before effective drug treatments were available.

The high mortality rate from TB without treatment underscores the importance of early diagnosis and prompt initiation of appropriate therapy. It also highlights the need to prevent the transmission of TB infection and the development of drug resistance. Without treatment, people with TB not only suffer from poor health and reduced quality of life, but also pose a risk to others by spreading the infection.

Fortunately, effective drug treatments for TB have been available for decades, and can cure most cases of drug-susceptible TB. However, some forms of TB are resistant to the standard drugs, and require longer and more complex regimens that are less effective and more toxic. Therefore, it is essential to ensure that people with TB receive the correct diagnosis and the best available treatment, and that they adhere to the prescribed regimen until they are cured. This will not only save lives, but also prevent the emergence and spread of drug-resistant TB.

TB is a curable disease if diagnosed and treated properly. The standard treatment for drug-susceptible TB consists of a 6-month regimen of four first-line drugs: isoniazid, rifampicin, ethambutol and pyrazinamide. These drugs kill the TB bacteria and prevent them from developing resistance. The treatment regimen is divided into two phases: an intensive phase of 2 months, followed by a continuation phase of 4 months. During the intensive phase, all four drugs are taken daily under direct observation of a health worker or a trained volunteer. This ensures adherence to the treatment and reduces the risk of defaulting or interrupting the therapy. During the continuation phase, only isoniazid and rifampicin are taken daily or thrice weekly, depending on the national guidelines.

The cost of the first-line drugs for TB treatment is relatively low, thanks to the efforts of the Global TB Drug Facility (GDF), which was established in 2001 to ensure access to quality-assured and affordable anti-TB drugs. The GDF supplies a complete 6-month course for about US$ 40 per person. However, the total cost of TB treatment also includes other expenses, such as diagnostic tests, health care visits, hospitalization, transportation, food supplements and social support. These costs can vary widely depending on the country and the health system. According to a WHO report in 2017 , the average total cost of TB treatment per patient ranged from US$ 88 in Ethiopia to US$ 887 in Brazil.

The treatment for drug-resistant TB (DR-TB) is more complex, longer and more expensive than that for drug-susceptible TB. DR-TB occurs when the TB bacteria become resistant to one or more of the first-line drugs, either due to inappropriate or incomplete treatment, poor quality of drugs, or transmission from another person with DR-TB. The most common forms of DR-TB are rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB), which are resistant to both isoniazid and rifampicin. There are also cases of extensively drug-resistant TB (XDR-TB), which are resistant to at least four of the most effective anti-TB drugs.

The standard treatment for DR-TB consists of a longer regimen of at least 9 months, which includes second-line drugs that are less effective, more toxic and more costly than the first-line drugs. Some of these drugs have serious side effects, such as hearing loss, kidney damage and psychosis. The treatment regimen is also divided into two phases: an intensive phase of at least 6 months, followed by a continuation phase of at least 3 months. During both phases, all drugs are taken daily under direct observation.

The cost of the second-line drugs for DR-TB treatment is much higher than that of the first-line drugs. The GDF supplies a complete 9-month course for about US$ 1000 per person. However, this does not include other costs, such as diagnostic tests for drug susceptibility testing (DST), monitoring tests for adverse reactions, health care visits, hospitalization and social support. According to a WHO report in 2017 , the average total cost of DR-TB treatment per patient ranged from US$ 4300 in Ethiopia to US$ 17 000 in Brazil.

The high cost of DR-TB treatment poses a major challenge for patients and health systems in low- and middle-income countries, where most cases occur. Many patients face catastrophic costs that push them into poverty or prevent them from completing their treatment. Moreover, many health systems lack the capacity and resources to provide adequate diagnosis and care for DR-TB patients. As a result, only about one in four people with DR-TB are diagnosed and enrolled in treatment globally , and only about half of them are successfully cured .

To address these challenges, WHO has recommended several strategies to improve the diagnosis and treatment of DR-TB . These include:

• The use of rapid molecular tests (such as Xpert MTB/RIF) to detect RR-TB and MDR-TB at the point of care
• The use of shorter regimens (9–12 months) for eligible patients with RR-TB or MDR-TB
• The use of new or repurposed drugs (such as bedaquiline and delamanid) for patients with RR-TB or MDR-TB who are not eligible for shorter regimens
• The use of individualized regimens based on DST results and patient history
• The provision of patient-centered care that includes psychosocial support, nutritional support and management of adverse reactions
• The implementation of infection control measures to prevent transmission of DR-TB
• The strengthening of surveillance systems to monitor trends and outcomes of DR-TB
• The promotion of research and development of new TB drugs and regimens

The treatment success rate is the percentage of people who are cured of TB or complete their treatment without evidence of failure. It is one of the indicators used to monitor the progress of TB control programs and the End TB Strategy.

According to the WHO Global Tuberculosis Report 2021, the global treatment success rate for drug-susceptible TB was 83% in 2019, which is close to the target of 90% by 2025. However, there was considerable variation across regions and countries, ranging from 71% in the Eastern Mediterranean Region to 91% in the Western Pacific Region. The main reasons for unsuccessful treatment outcomes were loss to follow-up (8%), death (6%) and failure (2%).

The treatment success rate for drug-resistant TB (DR-TB) was much lower than for drug-susceptible TB. In 2018, the latest year for which data are available, the global treatment success rate for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) was 59%, up from 50% in 2012. The treatment success rate for MDR/RR-TB varied widely across regions and countries, from 40% in the African Region to 72% in the European Region. The main reasons for unsuccessful treatment outcomes were loss to follow-up (18%), death (15%) and failure (7%).

Treatment for DR-TB is longer, more expensive and more toxic than for drug-susceptible TB. It requires second-line drugs, such as bedaquiline and fluoroquinolones, which may cause serious adverse events. The treatment success rate for extensively drug-resistant TB (XDR-TB), which is resistant to the most effective second-line drugs, was even lower at 30%.

To improve the treatment success rates for DR-TB, WHO recommends the use of all-oral regimens that include newer drugs such as bedaquiline and linezolid, as well as shorter regimens for selected patients with MDR/RR-TB. WHO also advises countries to monitor and manage adverse events, ensure patient support and adherence, and strengthen laboratory capacity and surveillance of drug resistance.

Despite the availability of effective drug treatments for TB, the disease remains a major global health problem. One of the challenges is the emergence and spread of drug-resistant TB, which requires longer and more complex regimens that are often less effective and more toxic. Another challenge is the lack of a vaccine that can prevent TB disease in adults, especially those who are at high risk of exposure or reactivation of latent infection.

To address these challenges, there is an urgent need for new TB drugs and vaccines that can shorten the duration of treatment, improve the outcomes of drug-resistant TB, and prevent TB infection and disease in all age groups. According to the WHO Global Tuberculosis Report 2018, there are 20 TB drugs in clinical trials, and 12 TB vaccines in Phase I, Phase II or Phase III trials.

Some of the promising new TB drugs that are being tested in clinical trials include:

• Bedaquiline and delamanid: These are the first new anti-TB drugs to be approved by regulatory authorities in over 40 years. They have shown activity against MDR-TB and are recommended by WHO as part of longer regimens for MDR-TB under certain conditions. They are also being evaluated in shorter and simpler regimens for MDR-TB and drug-susceptible TB.
• Pretomanid: This is a nitroimidazole compound that has potent activity against both drug-susceptible and drug-resistant TB. It is being tested in combination with bedaquiline and linezolid as a 6-month regimen for MDR-TB and extensively drug-resistant TB (XDR-TB).
• Sutezolid: This is an oxazolidinone derivative that has shown activity against both drug-susceptible and drug-resistant TB. It is being tested in combination with other drugs for MDR-TB and XDR-TB.
• Rifapentine: This is a rifamycin derivative that has a longer half-life than rifampicin and can potentially reduce the frequency of dosing. It is being tested in combination with other drugs for drug-susceptible TB and latent TB infection.

Some of the promising new TB vaccines that are being tested in clinical trials include:

• M72/AS01E: This is a subunit vaccine that contains two antigens from M. tuberculosis (M72) and an adjuvant (AS01E) that enhances the immune response. It has shown efficacy in preventing pulmonary TB disease in adults who are already infected with M. tuberculosis in a Phase IIb trial.
• MTBVAC: This is a live attenuated vaccine that is derived from a clinical isolate of M. tuberculosis that has been genetically modified to reduce its virulence. It has shown safety and immunogenicity in infants and adults in Phase I trials.
• BCG revaccination: This is a strategy of administering a second dose of BCG vaccine to individuals who have already received BCG at birth or early childhood. It has shown efficacy in preventing sustained M. tuberculosis infection in adolescents in a Phase II trial.

The development of new TB drugs and vaccines is a complex and costly process that requires collaboration among multiple stakeholders, including researchers, funders, regulators, policy-makers, health-care providers, and affected communities. The WHO plays a key role in setting global standards and guidelines, facilitating coordination and alignment, providing technical support, and monitoring progress and impact. The WHO End TB Strategy aims to end the global TB epidemic by 2035, with targets of reducing TB deaths by 95% and cutting new cases by 90%. Achieving these ambitious goals will depend on the availability and accessibility of new tools for diagnosis, treatment, and prevention of TB.

Challenges and opportunities for ending TB

The WHO Global Tuberculosis Report 2018 provides a comprehensive and up-to-date assessment of the TB epidemic, and of progress in prevention, diagnosis and treatment of the disease, at global, regional and country levels. The report also highlights the challenges and opportunities for ending TB by 2030, as envisioned by the WHO End TB Strategy and the UN Sustainable Development Goals.

Some of the main challenges include:

• The large gap between the estimated number of people who develop TB each year and the number who are diagnosed and reported to national authorities. In 2017, there were an estimated 10 million new cases of TB, but only 6.4 million were notified to WHO, leaving a gap of 3.6 million people who were either undiagnosed, unreported or both.
• The persistent burden of drug-resistant TB, which poses a serious threat to global health security. In 2017, there were an estimated 558 000 new cases of TB that were resistant to rifampicin (the most effective first-line drug), of which 82% had multidrug-resistant TB (MDR-TB). However, only 25% of these cases were detected and reported, and only 55% of those who started treatment for MDR-TB in 2016 were successfully treated.
• The low coverage and quality of preventive treatment for people at high risk of developing TB, such as household contacts of TB patients, people living with HIV and children under five years old. In 2017, only 23% of the eligible household contacts and 36% of the eligible people living with HIV received preventive treatment.
• The insufficient funding for TB care and prevention, especially from domestic sources in low- and middle-income countries. In 2018, the total funding available for TB was US$ 6.6 billion, which was US$ 3.5 billion less than the global target of US$ 10.1 billion for 2018 set in the End TB Strategy.
• The limited research and development for new tools and innovations to diagnose, treat and prevent TB. In 2017, the total funding for TB research was US$ 0.7 billion, which was only a quarter of the US$ 2.8 billion annual target set by the Stop TB Partnership.

Despite these challenges, there are also opportunities to accelerate progress towards ending TB, such as:

• The political commitment and momentum generated by the first-ever UN High-Level Meeting on TB in September 2018, which resulted in a political declaration endorsed by heads of state and government that contains ambitious targets and commitments for action on TB.
• The availability of new technologies and innovations to improve TB diagnosis, treatment and prevention, such as rapid molecular tests, shorter regimens for MDR-TB, new drugs and vaccines in development, digital health solutions and social protection schemes .
• The increasing engagement and empowerment of civil society, communities and people affected by TB to advocate for their rights and needs, to participate in decision-making processes and to monitor the quality and accountability of TB services.
• The potential synergies and benefits of integrating TB care and prevention with other health services and programmes, such as HIV/AIDS, maternal and child health, noncommunicable diseases, universal health coverage and antimicrobial resistance .

To seize these opportunities and overcome these challenges, WHO calls for urgent action from all stakeholders to scale up effective interventions, mobilize adequate resources, foster multisectoral collaboration and innovation, and ensure accountability for results.

We are Compiling this Section. Thanks for your understanding.