INTRODUCTION — An understanding of the epidemiology of Mycobacterium tuberculosis is critical for effective control. The global burden of tuberculosis (TB), risk factors for transmission, and the epidemiology of TB in the United States will be reviewed here. The epidemiology of drug-resistant TB is discussed separately. (See "Epidemiology and molecular mechanisms of drug-resistant tuberculosis".)
M. TUBERCULOSIS COMPLEX — M. tuberculosis is a member of the M. tuberculosis complex; other members include Mycobacterium africanum and Mycobacterium bovis.
M. africanum is most commonly found in West African countries; it causes up to a quarter of cases of TB in the Gambia [1]. The symptoms of infection resemble those of M. tuberculosis. The infectivity is similar to M. tuberculosis, and it is an important opportunistic pathogen in the setting of advanced immunosuppression due to human immunodeficiency virus (HIV) or other causes. Management is identical to management for disease due to M. tuberculosis.
M. bovis is discussed in detail separately. (See "Mycobacterium bovis".)
GLOBAL BURDEN
Epidemiology and socioeconomic factors — More than 1.7 billion people (approximately 22 percent of the world population) are estimated to be infected with M. tuberculosis [2,3]. The global incidence of TB peaked around 2003 and appears to be declining slowly [3]. According to the World Health Organization (WHO), in 2020, 9.9 million individuals became ill with TB and 1.5 million died [4].
The epidemiology of TB varies substantially around the world (figure 1 and table 1). The highest rates (300 per 100,000 or higher) are observed in sub-Saharan Africa, India, and the islands of Southeast Asia and Micronesia. Intermediate rates of TB (26 to 300 cases per 100,000) occur in China, Central and South America, Eastern Europe, and northern Africa. Low rates (less than 25 cases per 100,000 inhabitants) occur in the United States, Western Europe, Canada, Japan, and Australia.
Poverty, HIV, and drug resistance are major contributors to the resurging global TB epidemic [5,6]. Approximately 95 percent of TB cases occur in resource-limited countries. Approximately 1 in 12 new TB cases occur in individuals who are infected with HIV; 74 percent of these HIV-coinfected persons resided in Africa [3]. An estimated 465,000 cases of multidrug-resistant (MDR-) TB or rifampin-resistant TB also occurred in 2019.
Socioeconomic development and access to quality of health services appear to be at least as important as any specific TB control measure. The likelihood of success of TB control efforts is likely related to socioeconomic indicators, including gross domestic product per capita, mortality of children <5, access to clean water, and adequate sanitation and health expenditure per capita [7].
The importance of addressing these socioeconomic factors to achieve TB control is reinforced by the fact that many countries have experienced a rapid decline in TB burden without good access to high-quality TB treatment. In Europe, for example, TB morbidity and mortality declined long before effective chemotherapy was available, largely because of socioeconomic development, improved living conditions, better nutrition, and isolation of infectious cases in sanatoria [8].
Approach to global elimination
WHO "End TB" strategy — The WHO’s "End TB" strategy for 2016 to 2035 focuses on reducing deaths, reducing disease incidence, and reducing catastrophic costs due to TB (table 2). These TB goals were established as part of the Sustainable Development Goals (SDG) for 2016 to 2030 [9].
The new goals include a 90 percent reduction in TB deaths and an 80 percent reduction in TB incidence rate by 2030. Accomplishing these goals will require accelerating the decline in TB incidence from the current rate (1.5 to 2 percent) to 15 percent annually; such a decline could reduce the incidence of TB to <1 case per million by 2050. Achievement of this goal requires improvements in diagnosis, completion of disease treatment, and latent infection diagnosis and treatment.
The 2016 to 2035 SDGs for TB also recognize that TB treatment forces many patients and their families into poverty; thus, an additional important goal is that "no affected families face catastrophic costs related to TB."
Reasonable progress was made towards these goals in 2018 and 2019, but the coronavirus disease pandemic in 2019 and 2020 disrupted progress and will likely have a long-term negative impact [10].
Active case finding — The greatest barrier to reducing TB incidence and TB deaths is the substantial proportion of persons with TB disease that are never diagnosed and thus never treated. The WHO estimates that roughly 30 percent of such persons are never diagnosed [3]. Thus, efficient strategies for screening and treating these individuals, known as "active case finding," are needed.
Such programs need to screen for TB disease among patients not seeking health care for symptoms; approaches have included radiographic screening, sputum screening, and symptom surveys [11,12]. Interventions have targeted populations at increased risk including known contacts of individuals with active TB as well as individuals who are homeless, incarcerated, and/or HIV-infected.
The optimal approach to finding individuals with undiagnosed TB disease in high-incidence regions is uncertain; most cases occur in the absence of recognized risk factors [13]. In a cluster-randomized trial in Vietnam, active community-wide screening was compared with standard passive case detection (control) for reducing the prevalence of pulmonary TB among individuals ≥15 years, regardless of symptoms [14]. In 60 intervention clusters, active screening via sputum nucleic acid amplification testing (NAAT) was performed annually for three years, and antituberculous therapy was administered to patients diagnosed with TB; in 60 control clusters, no active screening was performed. In the fourth year, the prevalence of pulmonary TB was assessed via sputum NAAT (42,150 participants in the intervention group and 41,680 participants in the control group); active screening was associated with a lower prevalence of pulmonary TB than standard passive case detection alone (126 versus 225 per 100,000; prevalence ratio 0.56, 95% CI 0.40-0.78).
Further investigation is needed prior to broad implementation of active screening to assess the generalizability of these findings, the durability of the effect in endemic settings, and the feasibility of scaling up screening with NAATs.
LTBI screening and treatment — Controlling the TB epidemic also requires programs addressing the large burden of latent TB infection (LTBI); the 2015 WHO guidelines on LTBI management outline a strategy for identification and treatment of individuals with LTBI at increased risk for progression from latent infection to active disease [15]. These guidelines are aimed largely at middle- and upper-income countries; they recommend focusing efforts on case contacts and individuals with HIV infection, patients initiating anti-tumor necrosis factor treatment, patients receiving dialysis, patients preparing for organ or hematologic transplantation, and patients with silicosis. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)
Progress toward targets — By 2015, the millennium development goal target of reversing TB incidence was achieved, with TB incidence falling globally for several years beginning around 2006, at a rate of 1.5 to 2 percent per year [3]. Moreover, the global TB mortality rate has fallen by 45 percent since 1990. However, if the slow rate of decline in TB incidence and mortality is not accelerated, TB will continue to be a substantial source of global morbidity and mortality for decades.
An estimated 30 percent of patients with TB disease remain undiagnosed. Nearly half of the "missing cases" occur in Indonesia, India, and China [3]. Data on treatment success rates follow similar geographic patterns, although these rates reflect only the proportion of patients who received treatment. It is sometimes uncertain whether these patients completed an effective treatment course. The western Pacific and eastern Mediterranean have the greatest success (91 to 92 percent); other regions have fared less well (75 to 82 percent). Success is limited in part by the high prevalence of HIV infection in Africa and drug resistance in Eastern Europe.
Most patients who are coinfected with TB and HIV are not recognized to be coinfected. For example, the worldwide percentage of patients with TB disease who underwent subsequent HIV testing improved only marginally (from 1 to 55 percent) during the time period 2002 to 2015.
Detection and treatment of MDR-TB are also inadequate. The WHO estimates that only 44 percent of patients with MDR-TB were identified in 2019 and, of those, only 86 percent were started on second-line treatment.
IN THE UNITED STATES — Following a marked decline in the incidence of TB in the United States over several decades, the incidence rose in the period 1985 to 1992 [16,17]. Since 1992, there has been a substantial decline in the rate of TB; in 2014, it fell to a historic low of 2.9 per 100,000 (figure 2). In 2021, it was at 2.4 per 100,000, a 13 percent decrease from 2019 that may partially be attributable to the coronavirus disease 2019 (COVID-19) pandemic [18].
A majority of TB cases in the United States now occurs in foreign-born individuals emigrating from countries with high rates of endemic TB (71 percent of United States TB cases in 2021; the case rate in this group is 12.2 per 100,000) [18]. Of these cases, roughly half occur in individuals residing in the United States for ≤5 years [19]. Restriction fragment length polymorphism (RFLP) analysis has demonstrated that most of these cases are due to reactivation of latent infection rather than transmission within communities [20-25]. Therefore, screening for and treatment of latent infection can be a useful prevention tool among foreign-born individuals.
Increased travel and immigration of individuals from countries with endemic TB are certain to bring new challenges to TB control. In 2000, it was estimated that 11 million individuals with latent TB (with capacity for future reactivation) reside in the United States [26]. The countries accounting for the majority of cases of TB in foreign-born persons in the United States are Mexico, the Philippines, Vietnam, India, China, and the Dominican Republic and Haiti. The states accounting for the greatest number of United States cases are California, New York, New Jersey, Texas, and Florida (figure 3) [27,28].
According to data from the United States National TB Surveillance System, greater than 89 percent of TB patients in the United States received HIV testing in 2020; of these, 4.8 percent were HIV infected [29]. HIV infection rates in TB patients were highest among people who inject drugs, people who are homeless, correctional facility inmates, and people with an alcohol use disorder (35, 22, 16, and 15 percent, respectively) [30].
TB in the United States has been shown to be seasonal, with a peak in the spring and a trough in the fall [31]. Latitude-dependent factors, including reduced winter sunlight and its potential effect on vitamin D levels, do not appear to contribute significantly to seasonality in the United States. Instead, seasonality appears to be greater among clustered cases and children, groups in whom disease likely reflects recent transmission of TB. Therefore, TB disease resulting from recent infection with early progression to disease appears to be more influenced by season than disease that results from activation of latent TB.
RISK FACTORS — Risk factors for TB may be divided as follows:
●Impaired immunity (host factors)
●Increased exposure to infectious persons (environmental factors)
Host factors — Categories of host factors are outlined in the following sections. The relative risk for selected risk factors is outlined below. The relative importance of different risk factors varies with prevalence of exposure across regions.
Immunosuppression
HIV infection — Among HIV-infected individuals, the risk of acquiring TB is 9 to 16 times that of HIV-uninfected individuals [32,33]. The magnitude of risk is likely variable depending on the degree of HIV-induced immunosuppression [27,34-36].
The WHO estimated 9.9 million new TB cases in 2020, 8 percent of whom were people living with HIV [3]. The 2020 estimated incidence of TB by country and the prevalence of HIV in TB cases by country are summarized in the figures (figure 4 and figure 1).
The global incidence of new TB cases among HIV-infected patients has declined marginally since 2005. Between 2004 and 2020, deaths have declined from just over 500,000 in 2004 to 214,000 in 2020, largely due to increasing access to antiretroviral therapy (ART).
A large proportion of the global burden of HIV-associated TB occurs in sub-Saharan Africa, with 74 percent of new cases of TB and 79 percent of deaths. The burden is particularly high in southern Africa, where some countries have annual TB incidence rates exceeding 1000 per 100,000 population.
Dual infection with HIV and TB leads to reciprocal interactions that have significant clinical impact, as discussed in the following sections.
Effect of HIV on TB — The risk of TB doubles within the first year of HIV seroconversion due to rapid depletion of TB-specific T helper cells [37-39]. Thereafter, the risk of TB progressively increases with declining immunity [33,40-42].
HIV-infected individuals appear to be more likely to acquire M. tuberculosis if exposed [43,44], and they are also at increased risk of developing active TB from reactivated latent infection [42]. In addition, HIV infection is a risk factor for accelerated progression of TB following exposure; in one study, the duration of TB disease prior to diagnosis was estimated to be three times shorter in HIV-infected patients than in HIV-uninfected patients [45]. HIV-infected persons starting ART are at particularly high risk for being diagnosed with TB disease; this is likely "unmasking" of clinically unrecognized disease [46-48].
The risk of disease and death from TB is substantially increased among HIV-infected individuals due to reactivation from pre-existing latent TB and in the setting of new TB infection with rapid progression of disease [49-53]:
●In low-incidence settings with low transmission risk, the rate of progression to active TB disease is 3 to 13 percent per year [33,42]; the higher risk occurs in patients with CD4 <200 [42]. In two nosocomial TB outbreaks described in the United States and Italy, the risk of TB disease following exposure was 37 to 50 percent in individuals with HIV infection and no known prior exposure [54,55].
●In high-incidence settings with high transmission risk, the likelihood of progression to active TB disease is generally higher. In tuberculin skin test-positive HIV-infected individuals, the incidence of active TB ranges from 3 to 21 per 100 person-years [56]. In a cohort of individuals with advanced HIV infection in South Africa, the incidence of active TB was 68 per 100 person-years, likely the result of new infection and prevalent latent TB infection [40].
The risk of TB transmission from HIV-infected patients with TB is lower than the risk of TB transmission from HIV-uninfected patients with TB; this is because of the shorter disease duration as well as the higher proportion of sputum smear-negative TB seen with HIV infection [57]. In addition, advanced HIV-related immunosuppression (CD4 ≤250 cells/mm3) has also been associated with reduced likelihood of TB transmission [58].
Effect of TB on HIV — TB appears to increase the risk of progression to acquired immunodeficiency syndrome (AIDS) or death [59,60]. The acceleration of HIV diseases by TB may occur via one or more of the following mechanisms:
●TB infection is associated with significant increases in HIV viremia [61]. HIV viremia usually declines after initiation of successful TB treatment [62]; however, persistently high levels of viremia have been observed in some cases despite initiation of effective antituberculous therapy [63,64].
●Generalized immune activation, due to TB infection, may increase the proportion of CD4 cells that are preferential targets for HIV [65].
●Increased expression of the HIV co-receptors CCR5 and CXCR4 occurs in HIV-infected patients with TB coinfection [63].
Impact of ART on TB incidence — Despite unmasking of TB seen soon after initiation of antiretroviral therapy (ART), the long-term risk of TB decreases with initiation of ART [66-76]:
●In a randomized trial including more than 800 HIV-infected patients with baseline CD4 count between 200 and 350 cells/mm3 randomized to "early ART" (within two weeks of enrollment) or "deferred ART" (ART initiated based on time to onset of clinical AIDS or attainment of a CD4 cell count <200 cells/mm3), patients who received early ART had lower rate of incident TB than those who received deferred ART (18 versus 36 cases; hazard ratio [HR] 2.0, 95% CI 1.2-3.6) [76].
●In an observational study in South Africa including more than 1500 patients on ART, TB incidence in patients with CD4 count <100 and CD4 count >700 cells/mm3 was 26 and 3 per 100 person-years, respectively [73]. The TB incidence among patients with CD4 >700 cells/mm3 was 4.4-fold higher than the incidence in HIV-uninfected individuals from the same community; however, this is likely an overestimate as TB case ascertainment was high in this cohort.
Risk for relapse and recurrence — HIV-infected patients have an increased risk of recurrent TB after successful therapy, usually due to exogenous reinfection [77-79]. In one study including more than 580 culture-positive episodes of TB, recurrent TB was more common among HIV-infected patients than in HIV-uninfected patients; reinfection accounted for 12 of 23 in HIV-infected individuals and 1 of 16 recurrences among HIV-uninfected patients [80].
Patients with an initial episode of TB represent a susceptible population at high risk for a second infection with a new strain. In one study including 342 HIV-infected and 321 HIV-uninfected miners in South Africa, rates of recurrent TB (more than two years after the initial episode) were 24 and 4 percent, respectively [78]. Rates of recurrent TB were higher than rates of initial infection.
Low CD4 lymphocyte count is a key risk factor for relapse [81,82]. Among HIV-uninfected patients, cavitation and positive culture after two months of treatment are predictors of subsequent relapse among HIV-uninfected patients [83]; these may also be predictors among HIV-infected patients but have been less well studied.
Other forms of immunosuppression
●Glucocorticoids – Patients receiving a daily dose of ≥15 mg of prednisone (or its equivalent) for ≥1 month are at increased risk for TB [84]. A case-control study in the United Kingdom including more than 16 million person-years of TB risk demonstrated that patients with TB were 4.9 times more likely to have been using glucocorticoids than those without TB [85]. A meta-analysis also suggests that inhaled corticosteroids increase the risk of TB [86].
●Diabetes – Patients with diabetes are at increased risk for developing active TB and experience worse treatment outcomes [87-90].
●Tumor necrosis factor (TNF) inhibitors – TNF-alpha inhibitors (used in the treatment of rheumatic diseases and inflammatory bowel disease) impair host resistance to TB. This issue is discussed in detail separately. (See "Risk of mycobacterial infection associated with biologic agents and JAK inhibitors".)
●Transplant – Renal, cardiac, liver, and allogeneic stem cell transplants are all associated with increased risk for TB [91-94]. The risk in allogeneic stem cell transplants is less than in solid organ transplant patients; there does not appear to be an increased risk of TB in autologous stem cell transplant patients.
Substance abuse — Substance abuse is the most commonly reported behavioral risk factor among patients with TB in the United States [95].
●Drug use – The epidemiologic factors associated with injection and non-injection drug use (eg, homelessness, incarceration) contribute to the high prevalence of TB among drug users [42,96-100].
●Tobacco – Cigarette smoking confers a relative risk of about 1.5 to 2 for the development of TB [101-105]. Smoking has been found to be associated with both risk of relapse of TB and TB mortality.
●Alcohol – The risk of active TB is substantially elevated in individuals who consume more than 40 g alcohol per day [106]. This may be due to the effect of alcohol and alcohol-related conditions on the immune system.
Nutritional status — Malnutrition is generally understood to be an important risk factor for TB, although the relation between impaired immunity due to malnutrition and risk of acquiring TB has not been well characterized [107-111].
●Underweight – Persons who are underweight (body mass index of <18.5) have increased risk for TB by a factor of 2.6 (1.2 to 4.8) [107,108].
●Vitamin D – Vitamin D plays an important role in macrophage activation and restriction of mycobacterial growth, and diminished serum vitamin D levels appear to increase risk for TB infection [112-119]. Among African immigrants in Australia, for example, individuals with latent or active TB were observed to have substantially lower serum vitamin D levels than those without TB [116]. Issues related to vitamin D and TB are discussed further separately. (See "Tuberculosis infection (latent tuberculosis) in children", section on 'Role of vitamin D'.)
●Iron status – Iron is an important growth factor for M. tuberculosis in macrophages and appears to play an important role in host susceptibility to TB infection [120].
Systemic diseases — The diseases discussed in this section have been noted to confer some degree of increased risk for TB reactivation. However, in some cases, it can be difficult to discern the relative risk of systemic diseases for development of active TB, since many studies were performed in areas where the prevalence of TB is relatively low.
●Silicosis – The risk of TB is increased among miners with silicosis. The mechanism is not fully understood but may be related to impairment of pulmonary macrophage function by silica crystals. The relative risk depends on the severity of the silicosis and has been estimated at 1.4 to 2.9 [121-123].
●Malignancy – The risk of TB is increased in patients with hematologic malignancies and head and neck cancer [124]. In a 25-year review of cancer patients in the United States, the rate of TB among patients with hematologic neoplasms was >200 cases per 100,000 persons, or about 40 times the rate among the general population. Among patients with head and neck cancer, the rate was >100 cases per 100,000 persons. It is important to note that these studies were performed in areas where the prevalence of TB is relatively low.
Patients with solid tumors other than head and neck cancer do not have an increased risk for TB; among these individuals, the rate paralleled that of the general population.
●Diabetes – The risk of developing TB increases with increasing diabetes severity [125,126]. A case-control study of 5290 patients demonstrated that poorly controlled diabetes confers a 2.9-fold increase in the risk of developing pulmonary TB; the risk associated with well-controlled diabetes was minimal [35]. The mechanism by which diabetes confers an altered immune response to M. tuberculosis is not fully understood but may be related in part to altered cytokine expression [127].
●Renal disease – The risk of TB among patients with chronic renal disease risk is 6.9 to 52.5 times that of individuals without renal disease [128,129]. Uremia causes reduced cellular immunity. Other factors that may diminish immunity in the setting of renal failure include malnutrition, vitamin D deficiency, and hyperparathyroidism.
●Gastric surgery – Gastric resection for peptic ulcer disease has been described as a risk factor for TB (relative risk 1.7 to 2.0) [130,131]. Although this procedure is no longer performed routinely, gastric bypass is a similar procedure that may confer similar risk [132]. The mechanism is not understood but may be related to loss of gastric acidity; however, the risk of TB among persons with gastric achlorhydria has not been studied.
●Celiac disease – Celiac disease (autoimmune inflammation of the small intestine) is a risk factor for TB; the mechanism is not fully understood but may be related to malabsorption [133]. In a study of two national registries, the risk of TB was significantly higher among 14,335 individuals with a prior diagnosis of celiac disease than among the 69,888 matched controls (hazard ratio 3.74).
●Cirrhosis – Two studies have demonstrated that cirrhosis is a risk factor for TB; one study evaluated persons largely affected by alcohol-associated cirrhosis [134] and a second in persons with cirrhosis largely resulting from chronic infectious hepatitis [135].
●COPD – Chronic obstructive pulmonary disease (COPD) is also a predisposing factor for TB. In two studies, COPD was associated with increased risk for TB of 2.2 (1.2 to 4.1) and 2.5 (2.2 to 2.8) [136,137]. However, some of this increased risk may be attributable to smoking or use of corticosteroids among persons with COPD.
Age and sex
●Age – In resource-limited settings, TB rates are highest among young adults, reflecting primary transmission in this age group. In the United States and other developed countries, the rate of TB among older adults is higher than among younger adults and children, reflecting reactivation disease, possibly attributable to impaired immunity with aging [138].
●Sex – Among HIV-uninfected individuals, the rate of TB is higher among males than females, beginning in the young adult years and persisting throughout life. This observation is thought to reflect more frequent TB exposure in the community among men than women [139].
Social and environmental factors
Household contacts — Close household contact with an individual with smear-positive pulmonary TB is the most important risk factor for TB [140,141]. In a study of TB contact investigation including 1080 smear-positive patients and their 6225 close contacts, 36 percent of contacts had positive tuberculin skin tests [142]; this compares with an expected skin test–positive rate of only 2.9 percent in the general population [26].
Birth in a TB-endemic area — The fraction of TB cases in the United States ascribed to foreign-born individuals increased from 22 to 58 percent between 1986 and 2007 and has continued to climb since then; by 2020, it was 71 percent (figure 2) [28,143,144]. The risk of TB is highest in the first five years after immigration but remains higher than the United States–born population for up to 20 years after arrival [19,145]. Seven countries account for the majority of cases of TB in foreign-born persons in the United States: Mexico, the Philippines, Vietnam, India, China, and the Dominican Republic and Haiti [19,143,146].
Overseas screening for TB among United States–bound immigrants and refugees is a high-yield intervention for identifying TB and could reduce the number of TB cases among foreign-born persons in the United States [147,148]. Between 1999 and 2005, the prevalence of smear-negative and latent TB cases among immigrants was 961 and 837 cases per 100,000, respectively; the prevalence of these entities among refugees was 1036 and 2838 per 100,000, respectively. Active pulmonary TB and latent TB were diagnosed in the United States in 7 and 1.6 percent of those with overseas diagnoses, respectively. The risk for reactivation of latent TB is highest just after entry into the United States but remains elevated for many years after arrival [149,150].
Community settings — In places where contact with infectious individuals may occur, risk for acquiring TB infection is increased [151]. Crowding and poor ventilation can increase the risk of transmission in such settings [152-159]. Those at risk for increased exposure include residents and employees of congregate settings such as hospitals, correctional facilities, nursing homes, and homeless shelters. Among 1289 inmates incarcerated in 16 Maryland prisons in 1997, the incidence of tuberculin skin conversion was 6.3 infections per 100 person-years [152]. (See "Tuberculosis transmission and control in health care settings".)
Socioeconomic status — TB has traditionally been associated with low socioeconomic status, which also may be associated with crowding, poor nutrition, poor access to medical care, public assistance, unemployment, and low education [160].
Minority groups — TB disease rates in the United States vary among demographic groups. In 2020, the disease incidence among non-United States-born White, Hispanic, Black, and Asian individuals was 2.8, 8.0, 15.3, and 21.7 per 100,000, respectively [144].
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SUMMARY
●More than 1.7 billion people are estimated to be infected with tuberculosis (TB). The global incidence of TB disease peaked around 2003 and appears to be declining slowly. The World Health Organization (WHO) estimated that the incidence of active disease in 2020 was 9.9 million new cases, an incidence rate of 127 per 100,000 persons. (See 'Global burden' above.)
●Poverty, HIV, and drug resistance fan the flames of the TB epidemic. Worldwide, about 95 percent of TB cases occur in resource-limited countries. Among all new TB cases in 2020, 8 percent were estimated to be HIV infected; 74 percent of these cases occur in Africa. In 2019, there were an estimated 465,000 cases of multidrug-resistant (MDR-) TB. (See 'Global burden' above.)
●HIV is a major driver of the global TB epidemic; HIV-infected persons are at increased risk of acquiring infection, at increased risk of progressing from infection to disease, and at increased risk of death, compared with HIV-uninfected persons. These risks can be greatly reduced by administration of antiretroviral therapy.
●In 2015, the WHO announced the “End TB” strategy, with new milestones and targets for 2025 and 2035 that could lead to substantial reductions in the global TB burden (table 2). (See 'WHO "End TB" strategy' above.)
●Socioeconomic development and access and quality of health services appear to be at least as important as any specific TB control measure. Risk factors for TB may be divided into issues related to host immunity (eg, immunologic defects that lead to increased susceptibility to infection) and issues related to environmental exposure to infection (eg, risk of exposure to a case of infectious TB). (See 'Epidemiology and socioeconomic factors' above and 'Risk factors' above.)
●A majority of TB cases in the United States occurs in foreign-born individuals emigrating from countries with high rates of endemic TB. (See 'In the United States' above.)
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