Latent tuberculosis

A state of tuberculosis infection without symptoms

"LTBI" redirects here. For the airport, see Eskişehir Airport.

Medical condition

Latent tuberculosis

Other names| Latent tuberculosis infection
Specialty| Infectious disease

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Latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI), is when a person is infected with Mycobacterium tuberculosis, but does not have active tuberculosis (TB). Active tuberculosis can be contagious while latent tuberculosis is not, and therefore it is not possible to get TB from someone with latent tuberculosis. Various treatment regimens are in use for latent tuberculosis. They generally need to be taken for several months.

## Epidemiology

[edit]

As of 2023, it is estimated that one quarter of the world's population has latent or active TB,[1] with TB estimated to have newly infected 10.8 million people per year.[2]

The spread of TB is uneven throughout the world, with approximately 80% of the population in many Asian and African countries testing positive on tuberculin tests, while only 5–10% of the US population tests positive.[3]

## Transmission

[edit]

### Latent disease

[edit]

It is not possible to catch TB from someone with LTB. In people who develop active TB of the lungs, also called pulmonary tB, the Mantoux test will often be positive. They are contagious and capable of passing the bacteria to others. TB can be transmitted by exhalation. Tiny droplets exhaled by someone with active TB can remain suspended in the air for several hours based on environmental conditions. Another person could then inhale the droplets and potentially become infected with TB. However, this is unlikely to occur, as infection generally requires longer exposure.[4] This includes brief exposures which happen when one is exposed to TB during brief social contact; prolonged exposure (over a couple of months, for example, by living with a relative with TB[5]) is generally required for TB infection.[6]

Statistics show that approximately one-third of people exposed to pulmonary TB become infected with the bacteria, but only one in ten of these infected people develop active TB disease during their lifetime.[7] People with latent TB are not contagious and will not feel sick. However, latent infections can become active TB infections, which are contagious, in the future.[8]

In some countries like Canada and the United States of America, people have medical privacy or "confidentiality" and do not have to reveal their active TB diagnosis to family, friends, or co-workers. A person will know they have been exposed to TB only through required testing for some jobs[9], developing symptoms of active TB, and visiting and testing by a medical doctor. Because TB is not common in the US, doctors may not suspect TB; therefore, they may not test for the infection. If a person has symptoms of TB, it is wise to be tested.[citation needed]

Persons with diabetes have a significantly higher chance of converting from latent to active TB,[10] and mortality from TB may be greater in diabetic patients.[10] Persons with both human immunodeficiency virus (HIV) and LTB have a 10% chance of developing active TB every year. "HIV infection is the greatest known risk factor for the progression of latent M. tuberculosis infection to active TB. In many African countries, 30–60% of all new TB cases occur in people with HIV, and TB is the leading cause of death globally for HIV-infected people."[11]

### Reactivation

[edit]

Once a person has been diagnosed with LTBI and a medical doctor confirms no active signs of infection or identifiable M. tuberculosis bacteria in the body, the person should remain alert to symptoms of active TB for the remainder of their life. Even after completing the full course of medication, there is no guarantee that all of the M. tuberculosis bacteria have all been killed.[12][13] "When a person develops active TB (disease), the symptoms (cough, fever, night sweats, weight loss, etc.) may be mild for many months. This can lead to delays in seeking care, and results in the transmission of the bacteria to others."[14]

TB bacteria may exist in the latent form both inside and outside of the lungs. In many cases, they may be latent in another organ, without any remaining bacteria in the lungs. If the reactivation of TB occurs in the brain, organs, kidneys, joints, or other areas, the symptoms are often slow to progress, frequently being ignored by patients until they become severe.[15][12] Extrapulmonary tuberculosis (TB outside of the lungs) can affect virtually any organ, with distinct manifestations depending on the site: TB in the spine causes back pain and potential paralysis; lymph node involvement presents as painless or occasionally painful swelling in the neck or armpits; meningeal infection triggers persistent headaches and altered consciousness; while urogenital tuberculosis leads to painful urination, blood in urine, and infertility. All of these may feature generalized symptoms like fever, night sweats, and weight loss, which, combined with their nonspecific presentation and lower amounts of bacteria, make them more difficult to diagnose than the classic pulmonary disease.[16][12]

### Risk factors

[edit]

Situations in which TB may become reactivated are:

* if there is onset of a disease affecting the immune system (such as acquired immunodeficiency syndrome [AIDS]) or a disease whose treatment affects the immune system (such as chemotherapy in cancer or systemic steroids in asthma or Enbrel, Humira, or Orencia in rheumatoid arthritis);[citation needed]
* malnutrition (which may be the result of illness or injury affecting the digestive system, a prolonged period of not eating, or disturbance in food availability such as during famine or residence in a refugee or concentration camp);
* degradation of the immune system due to aging;[17]
* certain systemic diseases such as diabetes,[18]
* other conditions such as debilitating disease (especially hematological and some solid cancers), use of long-term steroid medication, end-stage renal disease, silicosis, gastrectomy, and jejuno-ileal bypass;[19]
* being elderly;[20] and
* young age.[21]

### Concomitant immunity

[edit]

Compared to uninfected individuals, people with LTB appears to have some (35-80%) protection against developing active TB after being exposed to M. tuberculosis in the environment. This kind of protection is called concomitant immunity. It seems to be due to the presence of tissue-resident memory T cells.[22]

## Diagnosis

[edit]

There are two classes of tests commonly used to identify patients with LTB: tuberculin skin tests and Interferon-gamma(IFN-γ) tests.[citation needed]

The two tuberculin skin tests currently include the following:[citation needed]

* Mantoux test
* Heaf test

The three IFN-γ tests include the following:

* T-SPOT.TB
* QuantiFERON-TB Gold
* QuantiFERON-TB Gold In-Tube

### Tuberculin skin testing

[edit]

The tuberculin skin test (TST) in its first iteration, the Mantoux Test, was developed in 1908. Tuberculin (also called purified protein derivative or PPD) is a standardized dead extract of cultured TB, injected into the skin to measure the person's immune response to the bacteria. If a person has been exposed to the bacteria previously, they should express an immune reaction to the injection, usually a mild swelling or redness around the site. There have been two primary methods of TST: the Mantoux test and the Heaf test. The Heaf test was discontinued in 2005 because the manufacturer deemed its production to be financially unsustainable, though it was previously preferred in the United Kingdom (UK) because it may require less training to administer and involved less inter-observer variation in its interpretation than the Mantoux test. The Mantoux test was the preferred test in the US, and is now the most widely used TST globally.[citation needed]

#### Mantoux test

[edit]

See: Mantoux test

The Mantoux test is now standardized by the World Health Organization (WHO). Tuberculin at 0.1 milliliter (mL; 100 units/mL), which delivers a dose of 5 units, is given by intradermal injection into the surface of the lower forearm (subcutaneous injection results in false negatives). A waterproof ink mark is drawn around the injection site so as to avoid difficulty of finding it later if the level of reaction is small. The test is read 48 to 72 hours later.[23] The area of induration (NOT of erythema) is measured transversely across the forearm (left to right, not up and down) and recorded to the nearest millimeter (mm).[24]

#### Heaf test

[edit]

See: Heaf test

The Heaf test was first described in 1951.[25] The test uses a Heaf gun with disposable single-use heads; each head has six needles arranged in a circle. There are standard heads and pediatric heads: the standard head is used on all patients aged 2 years and older; the pediatric head is for infants under the age of 2 years old. For the standard head, the needles protrude 2 mm when the gun is actuated; for the pediatric heads, the needles protrude 1 mm. Skin is cleaned with alcohol, then tuberculin (100,000 units/mL) is evenly smeared on the skin (about 0.1 mL); the gun is then applied to the skin and fired. The excess solution is then wiped off and a waterproof ink mark is drawn around the injection site. The test is read 2 to 7 days later.[citation needed]

* Grade 0: no reaction, or induration of three or fewer puncture points;
* Grade 1: induration of four or more puncture points;
* Grade 2: induration of the six puncture points coalesce to form a circle;
* Grade 3: induration of 5 mm; or more
* Grade 4: induration of 10 mm or more, or ulceration

The results of both tests are roughly equivalent as follows:[citation needed]

* Heaf grade 0 & 1 ~ Mantoux less than 5 mm;
* Heaf grade 2 ~ Mantoux 5–14 mm;
* Heaf grade 3 & 4 ~ Mantoux 15 or greater

#### Tuberculin conversion

[edit]

Tuberculin conversion is said to occur if a patient who previously had a negative tuberculin skin test develops a positive tuberculin skin test at a later date. It indicates a change from negative to positive, and usually signifies a new infection.[citation needed]

#### Boosting

[edit]

The phenomenon of boosting is one way of obtaining a false positive test result. Theoretically, a person's ability to develop a reaction to the TST may decrease over time – for example, a person is infected with latent TB as a child and is administered a TST as an adult. Because there has been such a long time since the immune responses to TB has been necessary, that person might give a negative test result. If so, there is a fairly reasonable chance that the TST triggers a hypersensitivity response in the person's immune system and the body overreacts to what it perceives as a re-infection. In this case, when that person is given the test again (as is standard procedure, see above), they may have a significantly greater reaction to the test, giving a very strong positive; this can be commonly misdiagnosed as Tuberculin Conversion. This can also be triggered by receiving the BCG vaccine, as opposed to a proper infection. Although boosting can occur in any age group, the likelihood of the reaction increases with age.[26]

Boosting is only likely to be relevant if an individual is beginning to undergo periodic TSTs (health care workers, for example). In this case, the standard procedure is called two-step testing. The individual is given their first test and in the event of a negative, given a second test in 1 to 3 weeks. This is done to combat boosting in situations where, had that person waited up to a year to get their next TST, they might still have a boosted reaction, and be misdiagnosed as a new infection.[27]

There is a difference in US and UK guidelines. In the US, testers are told to ignore the possibility of false positive due to the BCG vaccine, as the BCG is seen as having waning efficacy over time. Therefore, the Centers for Disease Control and Prevention (CDC) urges that people be treated based on risk stratification regardless of BCG vaccination history, and if a person receives a negative and then a positive TST, they will be assessed for full TB treatment beginning with an X-ray to confirm that TB is not active and proceeding from there.[28] Conversely, the UK guidelines acknowledge the potential effect of the BCG vaccination, as it is mandatory and therefore a prevalent concern. Though the UK shares the procedure of administering two tests, 1 week apart, and accepting the second one as the accurate result, they also assume that a second positive is indicative of an old infection (and therefore, certainly LTBI) or the BCG itself. In the case of BCG vaccinations confusing the results, Interferon-γ (IFN-γ) tests may be used as they will not be affected by the BCG.[citation needed]

#### Interpretation

[edit]

According to the US guidelines, there are multiple size thresholds for declaring a positive result of LTB from the Mantoux test: For people from high-risk groups, such as those who are HIV positive, the cutoff is 5 mm of induration; for medium risk groups, 10 mm; for low-risk groups, 15 mm. The US guidelines recommend that a history of previous BCG vaccination should be ignored. For details of tuberculin skin test interpretation, please refer to the CDC guidelines (reference given below).

The UK guidelines are formulated according to the Heaf test: In people who have had BCG previously, LTB is diagnosed if the Heaf test is grade 3 or 4, and people have no signs or symptoms of active TB. If the Heaf test is grade 0 or 1, then the test is repeated. In people who have not had BCG previously, latent TB is diagnosed if the Heaf test is grades 2, 3, or 4, and have no signs or symptoms of active TB. Repeat Heaf testing is not done in patients who have had BCG (because of the phenomenon of boosting). For details of tuberculin skin test interpretation, please refer to the BTS guidelines (references given below).

Given that the US recommendation is that prior BCG vaccination be ignored in the interpretation of tuberculin skin tests, false positives with the Mantoux test are possible as a result of: (1) having previously had a BCG vaccine (even many years ago), or (2) periodical testing with tuberculin skin tests. Having regular TSTs boosts the immunological response in those people who have previously had BCG, so these people will falsely appear to be tuberculin conversions. This may lead to treating more people than necessary, with the possible risk of those people developing adverse drug reactions. However, as Bacille Calmette-Guérin vaccine is not 100% effective, and is less protective in adults than pediatric patients, not treating these people could lead to a possible infection. The current[when?] US policy seems to reflect a choice to focus infection control.

The US guidelines also allow for tuberculin skin testing in immunosuppressed people (those with HIV, or who are on immunosuppressive drugs), whereas the UK guidelines recommend that tuberculin skin tests should not be used for such people because it is unreliable.[citation needed]

### Interferon-γ testing

[edit]

The role of IFN-γ tests is undergoing constant review and various guidelines have been published with the option for revision as new data becomes available.CDC:MMWR Health Protection Agency:UK

There are currently two commercially available interferon-γ release assays (IGRAs): QuantiFERON-TB Gold and T-SPOT.TB.[29] These tests are not affected by prior BCG vaccination, and assess the body's response to specific TB antigens not present in other forms of mycobacteria and BCG (ESAT-6). Whilst these tests are new, they are now becoming available globally.

CDC:

> CDC recommends that QFT-G may be used in all circumstances in which the TST is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers).

HPA Interim Guidance:

> The HPA recommends the use of IGRA testing in health care workers, if available, in view of the importance of detecting latently infected staff who may go on to develop active disease and come into contact with immunocompromised patients and the logistical simplicity of IGRA testing.

### Drug-resistant strains

[edit]

It is usually assumed by most medical practitioners that in the early stages of a diagnosis, a case of LTB is the normal or regular strain of TB. It will therefore be most commonly treated with Isoniazid (the most used treatment for LTB.) Only if the TB bacteria does not respond to the treatment will the medical practitioner begin to consider more virulent strains, requiring significantly longer and more thorough treatment regimens.[citation needed]

There are four types of TB recognized in the world today:[citation needed]

* TB
* Multi-drug-resistant tuberculosis (MDR TB)[30]
* Extensively drug-resistant tuberculosis (XDR TB)[31]
* Totally drug-resistant tuberculosis (TDR TB)[32]

## Treatment

[edit]

Main article: Tuberculosis treatment

The treatment of LTBI is essential to controlling and eliminating TB by reducing the risk that TB infection will progress to disease. LTB will convert to active TB in 10% of cases (or more in cases of immunocompromised patients). Taking medication for LTB is recommended by many doctors.[33]

In the US, the standard treatment is 9 months of isoniazid, but this regimen is not widely used outside of the US.[citation needed]

### Terminology

[edit]

There is no agreement regarding terminology: the terms preventive therapy and chemoprophylaxis have been used for decades, and are preferred in the UK because it involves giving medication to people who have no disease and are currently well: the reason for giving medication is primarily to prevent people from becoming unwell. In the US, physicians talk about LTB treatment because the medication does not actually prevent infection: the person is already infected and the medication is intended to prevent existing silent infection from becoming active disease. There are no convincing reasons to prefer one term over the other.[citation needed]

### Specific situations

[edit]

"Populations at increased risk of progressing to active infection once exposed:[citation needed]

* Persons with recent TB infection [those infected within the previous 2 years]
* Congenital or acquired immunosuppressed patients (in particular, HIV-positive patients)
* Illicit intravenous drug users; alcohol and other chronic substance users
* Children (particularly those younger than 4 years old)
* Persons with comorbid conditions (i.e., chronic kidney failure, diabetes, malignancy, hematologic cancers, body weight of at least 10% less than ideal, silicosis, gastrectomy, jejunoileal bypass, asthma, or other disorders requiring long-term use of corticosteroids or other immunosuppressants)."[34]

### Treatment regimens

[edit]

It is essential that assessment to rule out active TB be carried out before treatment for LTBI is started. To give treatment for LTB to someone with active TB is a serious error: the TB will not be adequately treated and there is a serious risk of developing drug-resistant strains of TB.

There are several treatment regimens currently in use:

* 9H — isoniazid for 9 months is the gold standard (93% effective, in patients with positive test results and fibrotic pulmonary lesions compatible with TB[35]).
* 6H — Isoniazid for 6 months might be adopted by a local TB program based on cost-effectiveness and patient compliance. This is the regimen currently recommended in the UK for routine use. The US guidance excludes this regimen from use in children or persons with radiographic evidence of prior TB (old fibrotic lesions) (69% effective).
* 6 to 9H2 — An intermittent twice-weekly regimen for the above two treatment regimens is an alternative if administered under Directly observed therapy (DOT).
* 4R — rifampicin for 4 months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant TB.
* 3HR — Isoniazid and rifampin may be given daily for 3 months.
* 2RZ — The 2-month regimen of rifampin and pyrazinamide is no longer recommended for treatment of LTBI because of the greatly increased risk of drug-induced hepatitis and death.[36]
* 3HP – 3-month (12-dose) regimen of weekly rifapentine and isoniazid.[37][38] The 3HP regimen has to be administered under DOT. A self-administered therapy (SAT) of 3HP is investigated in a large international study.[39]

### Evidence for treatment effectiveness

[edit]

A 2000 Cochrane review containing 11 double-blinded, randomized control trials and 73,375 patients examined 6 and 12-month courses of isoniazid (INH) for treatment of LTB. HIV positive and patients currently or previously treated for TBs were excluded. The main result was a relative risk (RR) of 0.40 (95% confidence interval [CI] 0.31 to 0.52) for development of active TB over 2 years or longer for patients treated with INH, with no significant difference between treatment courses of 6 or 12 months (RR 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months).[40]

A Cochrane systematic review published in 2013 evaluated four different alternatives regimens to INH monotherapy for preventing active TB in HIV-negative people with LTB infection. The evidence from this review found no difference between shorter regimens of rifampicin or weekly, and directly observed how Rifapentine plus INH compared to INH monotherapy in preventing active TB in at-ick HIV-negative people. However, the review found that the shorter rifampicin regimen for 4 months and weekly directly observed Rifapentine plus INH for 3 months "may have additional advantages of higher treatment completion and improved safety." However the overall quality of evidence was low to moderate (as per GRADE criteria) and none of the included trials were conducted in low- to middle-income countries (LMIC) with high TB transmission and hence might not be applicable to nations with high TB transmission.[41]

### Treatment efficacy

[edit]

There is no guaranteed "cure" for LTB. "People infected with TB bacteria have a lifetime risk of falling ill with TB..."[14] with those who have compromised immune systems, those with diabetes and those who use tobacco at greater risk.[14]

A person who has taken the complete course of Isoniazid (or other full course prescription for TB) on a regular, timely schedule may have been cured. "Current standard therapy is isoniazid (INH) which reduces the risk of active TB by as much as 90 percent (in patients with positive LTBI test results and fibrotic pulmonary lesions compatible with tuberculosis[35]) if taken daily for 9 months."[40] However, if a person has not completed the medication exactly as prescribed, the "cure" is less likely, and the "cure" rate is directly proportional to following the prescribed treatment specifically as recommended. Furthermore, "If you don't take the medicine correctly and you become sick with TB a second time, the TB may be harder to treat if it has become drug resistant."[15] If a patient were to be cured in the strictest definition of the word, it would mean that every single bacterium in the system is removed or dead, and that person cannot get TB (unless re-infected). However, there is no test to assure that every single bacterium has been killed in a patient's system. As such, a person diagnosed with LTB can safely assume that, even after treatment, they will carry the bacteria – likely for the rest of their lives. Furthermore, "It has been estimated that up to one-third of the world's population is infected with M. tuberculosis, and this population is an important reservoir for disease reactivation."[41] In areas where TB is endemic, treatment may be even less certain to "cure" TB, as reinfection could trigger activation of LTB already present even in cases where treatment was followed completely.[citation needed]

## Controversy

[edit]

There is controversy over whether people who test positive long after infection have a significant risk of developing the disease (without re-infection). Some researchers and public health officials have warned that this test-positive population is a "source of future TB cases" even in the US and other wealthy countries, and that this "ticking time bomb" should be a focus of attention and resources.[42]

On the other hand, Marcel Behr, Paul Edelstein, and Lalita Ramakrishnan reviewed studies concerning the concept of LTB in order to determine whether TB-infected persons have life-long infection capable of causing disease at any future time. These studies, both published in the British Medical Journal (BMJ) in 2018 and 2019, show that the incubation period of TB is short, usually within months after infection, and very rarely more than 2 years after infection.[43][44] They also show that more than 90% of people infected with M. tuberculosis for more than 2 years never develop TB even if their immune system is severely suppressed.[45] Immunologic tests for TB infection such as the tuberculin skin test and IGRAs only indicate past infection, with the majority of previously infected persons no longer capable of developing TB. Ramakrishnan told the New York Times that researchers "have spent hundreds of millions of dollars chasing after latency, but the whole idea that a quarter of the world is infected with TB is based on a fundamental misunderstanding."[46]

Writing in The Atlantic, science journalist Katherine J. Wu explains:[47]

> If the bacteria were lingering, researchers would expect to see a big spike in disease late in life among people with positive skin tests, as their immune system naturally weakens. They would also expect to see a high rate of progression to full-blown TB among people who start taking immunosuppressive drugs or catch HIV. And yet, neither of those trends pans out: At most, some 5 to 10 percent of people who have tested positive by skin test and later sustain a blow to their immune system develop TB disease within about three to five years—a hint that, for almost everyone else, there may not be any MTB left. “If there were a slam-dunk experiment, that’s it,” William Bishai, a TB researcher at Johns Hopkins, told me.

The first BMJ article disputing widespread latency was accompanied by an editorial written by Dr. Soumya Swaminathan, Deputy Director-General of the World Health Organization, who endorsed the findings and called for more funding of TB research directed at the most heavily afflicted parts of the world, rather than disproportionate attention to a relatively minor problem that affects just the wealthy countries.[46]

The WHO no longer endorses the concept that all those with immunologic evidence of past TB infection are currently infected and so are at risk of developing TB some time in the future. In 2022, the WHO issued corrigenda to its 2021 Global TB Report to clarify estimates on the worldwide burden of infected people.[48] These corrigenda deleted "About a quarter of the world's population is infected with M. tuberculosis" and replaced it with "About a quarter of the world's population has been infected with M. tuberculosis." The corrigenda also removed the prior estimate of the lifetime risk of TB of 5 to 10% among those with evidence of past TB infection, indicating that they no longer have confidence in earlier estimates that a substantial percentage of those with positive immunologic test results will develop the disease.

## See also

[edit]

* Silent disease

## References

[edit]

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35. ^ a b Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bull World Health Organ. 1982;60(4):555-64.
36. ^ Schechter M, Zajdenverg R, Falco G, Barnes G, Faulhaber J, Coberly J, Moore R, Chaisson R (2006). "Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts". Am J Respir Crit Care Med. 173 (8): 922–6\. doi:10.1164/rccm.200512-1953OC. PMC 2662911. PMID 16474028.
37. ^ Timothy R. Sterling; M. Elsa Villarino; Andrey S. Borisov; Nong Shang; Fred Gordin; Erin Bliven-Sizemore; Judith Hackman; Carol Dukes Hamilton; Dick Menzies; Amy Kerrigan; Stephen E. Weis; Marc Weiner; Diane Wing; Marcus B. Conde; Lorna Bozeman; C. Robert Horsburgh, Jr.; Richard E. Chaisson (2011). "Three months of rifapentine and isoniazid for latent tuberculosis infection". New England Journal of Medicine. 365 (23): 2155–2166\. doi:10.1056/NEJMoa1104875. PMID 22150035. S2CID 36515489.
38. ^ Recommendations for Use of an Isoniazid-Rifapentine Regimen with Direct Observation to Treat Latent Mycobacterium tuberculosis Infection Archived 2022-09-01 at the Wayback Machine. cdc.gov. updated November 22, 2013.
39. ^ Clinical trial number NCT01582711 for "Study 33: Adherence to Latent Tuberculosis Infection Treatment 3HP SAT Versus 3HP DOT (iAdhere)" at ClinicalTrials.gov
40. ^ a b Menzies, Dick; Al Jahdali, Hamdan; Al Otaibi, Badriah (2011). "Recent developments in treatment of latent tuberculosis infection". The Indian Journal of Medical Research. 133 (3): 257–66\. PMC 3103149. PMID 21441678.
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42. ^ Maugh II, Thomas H. (2011-05-17). "Shorter treatment found for latent tuberculosis". Los Angeles Times. Archived from the original on 2022-08-19. Retrieved 2019-10-29. "Although TB control measures in the United States have brought the incidence of the disease to an all-time low of 11,181 cases in 2010, it is estimated that at least 11 million Americans have latent TB. 'The 11 million Americans with latent TB represent a ticking time bomb,' Dr. Kenneth Castro, director of the Centers for Disease Control and Prevention's division of tuberculosis elimination, said at a news conference Monday. 'They're the source of future TB cases.'"
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44. ^ Behr, Marcel A.; Edelstein, Paul H.; Ramakrishnan, Lalita (2024). "Rethinking the burden of latent tuberculosis to reprioritize research". Nature Microbiology. 9 (5): 1157–1158\. doi:10.1038/s41564-024-01683-0. PMID 38671272.
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46. ^ a b McNeil, Donald G. Jr. (20 September 2018). "'Latent' tuberculosis? It's not that common, experts find". The New York Times. Archived from the original on 17 August 2022. Retrieved 13 March 2020.
47. ^ Wu, Katherine J. (2023). "A big misconception about the world's greatest infectious killer". The Atlantic.
48. ^ Corrigenda (25 May 2022) Global tuberculosis report 2021 (PDF). World Health Organization. 14 October 2021. ISBN 978-92-4-003702-1. Archived (PDF) from the original on 8 August 2022. Retrieved 18 September 2022.

This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention.

## Further reading

[edit]

* Jasmer, R. M.; Nahid, P.; Hopewell, P. C. (2002). "Latent tuberculosis infection". New England Journal of Medicine. 347 (23): 1860–1866\. doi:10.1056/NEJMcp021045. PMID 12466511.
* Mazurek, G. H.; Villarino, M. E. (2003). "Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection". Morbidity and Mortality Weekly Report. 52 (RR–2): 15–18.
* Ormerod, P.; Skinner, C.; Moore-Gillon, J.; Davies, P.; Connolly, M. (2000). "BTS Guidelines: control and prevention of tuberculosis in the United Kingdom: Code of Practice 2000". Thorax. 55 (11): 887–901\. doi:10.1136/thorax.55.11.887. PMC 1745632. PMID 11050256.

## External links

[edit]

Classification|

* ICD-10: R76.1
* MeSH: D055985

|

* v
* t
* e

Blood film findings

Red blood cells|

| Size|

* Anisocytosis
* Macrocytosis
* Microcytosis

|

Shape|

* Poikilocytosis
* Membrane abnormalities
* Acanthocyte
* Codocyte
* Elliptocyte
* Hereditary elliptocytosis
* Spherocyte
* Hereditary spherocytosis
* Dacrocyte
* Echinocyte
* Schistocyte
* Degmacyte
* Sickle cell/drepanocyte
* Sickle cell disease
* Stomatocyte
* Hereditary stomatocytosis

Colour|

* Anisochromia
* Hypochromic anemia
* Polychromasia

Inclusion bodies|

* Developmental
* Howell–Jolly body
* Basophilic stippling
* Pappenheimer bodies
* Cabot rings
* Hemoglobin precipitation
* Heinz body

Other|

* Haemoconia
* Red cell agglutination
* Rouleaux

White blood cells|

| Lymphocytes|

* Reactive lymphocyte
* Smudge cell
* Russell bodies

|

Granulocytes|

* Hypersegmented neutrophil
* Arneth count
* Pelger–Huët anomaly
* Döhle bodies
* Toxic granulation
* Toxic vacuolation
* Critical green inclusion
* Alder–Reilly anomaly
* Jordans' anomaly
* Left shift

Other|

* Auer rod

* v
* t
* e

Tuberculosis

Symptoms, signs and
associated conditions|

* Pulmonary tuberculosis
* Ghon focus / Ghon's complex
* Extrapulmonary tuberculosis
* Pott disease
* Canga's bead symptom
* Prosector's wart
* Lupus vulgaris
* Tuberculous lymphadenitis
* Tuberculous meningitis
* Miliary tuberculosis
* Urogenital tuberculosis
* Latent tuberculosis
* Caseous necrosis
* Paronychia
* Giant multinucleated cell
* Post-tuberculosis lung disease

Mycobacterium species|

* Mycobacterium africanum
* Mycobacterium bovis
* Mycobacterium caprae
* Mycobacterium tuberculosis

Tuberculosis diagnosis|

* Ziehl–Neelsen stain
* Auramine phenol stain
* Culture on Löwenstein–Jensen medium and/or MGIT
* Chest photofluorography
* GeneXpert MTB/RIF
* Interferon gamma release assay
* QuantiFERON
* T-SPOT.TB
* Microscopic Observation Drug Susceptibility assay
* Tuberculin
* Heaf test
* Mantoux test
* Tine test

Management
(ATC code J04)|

* Isoniazid
* 4-Aminosalicylic acid
* Ethambutol
* Capreomycin
* Cycloserine
* Rifampicin
* Thioacetazone
* Streptomycin
* Bedaquiline
* Pyrazinamide
* Rifater

Vaccines|

* BCG vaccine
* Experimental
* M72/AS01E
* MVA85A
* RBCG30

Resistance|

* Multidrug-resistant tuberculosis
* Extensively drug-resistant tuberculosis
* Totally drug-resistant tuberculosis

History of tuberculosis|

* Manuel de Abreu
* Hermann Brehmer
* Albert Calmette
* Christopher Dye
* Marcos Espinal
* Friedrich Franz Friedmann
* Max Gerson
* Alan L. Hart
* Philip D'Arcy Hart
* F. R. G. Heaf
* George M. Heath
* Robert Koch
* Charles Mantoux
* Richard Morton
* Mario Raviglione
* Carl Rüedi
* Lucius Rüedi
* Madonna Swan
* Edward Livingston Trudeau

Organizations|

* Adirondack Cottage Sanitarium
* Campaign for Access to Essential Medicines
* Center for Global Infectious Disease Research
* Cure Cottages of Saranac Lake
* European and Developing Countries Clinical Trials Partnership
* Glen Lake Children's Camp
* Glen Lake Sanatorium
* Glenn Dale Hospital
* The Global Fund to Fight AIDS, Tuberculosis and Malaria
* Global Plan to Stop Tuberculosis
* International Congress on Tuberculosis
* International Union Against Tuberculosis and Lung Disease
* Millennium Foundation
* Mycobacterium Tuberculosis Structural Genomics Consortium
* National Jewish Health
* Phipps Institute for the Study, Treatment and Prevention of Tuberculosis
* Stop TB Partnership
* TB Alliance
* Unitaid

Other|

* Tuberculosis elimination
* 2007 tuberculosis scare
* Baumgarten-Tangl law
* CFP-10
* ESAT-6
* Iowa Cow War
* List of tuberculosis cases
* N95 respirator
* Plombage
* Preventorium
* Sanatorium
* Sunshine Way
* Tuberculosis classification
* Tuberculosis in China
* Tuberculosis in human culture
* Tuberculosis radiology
* Tygerberg score
* World Tuberculosis Day

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