News in Brief: Body & Brain

Ear infection mix

What’s living in children’s noses could determine whether they get ear infections. Researchers from Yale and the University of Pennsylvania took swabs from the noses of sick children with and without ear infections. Kids with ear infections were more likely to carry Streptococcus pneumoniae bacteria, a major cause of pneumonia and ear infections. Some other types of bacteria seemed to protect against both Streptococcus and ear infections, the researchers reported online February 1 in mBio. Yet other types of bacteria promoted ear infection, including types that don’t cause ear infections themselves. The findings could lead to new ways to prevent ear infections.
Fiber may boost longevity

A high-fiber diet may contribute to a longer life, scientists report February 14 in the Archives of Internal Medicine. Researchers consulted data from more than 380,000 men and women who completed diet questionnaires in the 1990s. By tracking death records over nine years, scientists from the National Cancer Institute in Rockville, Md., determined that people consuming the most fiber were about 20 percent less likely to die of any cause during the study than people getting the least. Fiber from grains outweighed fiber from fruits, vegetables or beans in both men and women — but particularly in men..
Lavender oil vs. fungus

Lavender oil can knock out drug-resistant fungi called dermatophytes, lab-dish tests show. Distilled from the Iberian shrub Lavandula viridis L’Hér, the oil inhibited dermatophytes by attacking their cell membranes. It also proved promising against Candida fungi. Dermatophytes cause athletes’ foot, ringworm and nail infections, while Candida causes yeast infections. Researchers at the University of Coimbra in Portugal report the results in an upcoming issue of the Journal of Medical Microbiology. The active ingredient in the lavender oil appears to be an organic compound called alpha-pinene, they note. More tests are planned.

ALS on the move

Harmful proteins responsible for progressive, fatal ALS, or Lou Gehrig’s disease, can quickly hop from nerve cell to nerve cell, researchers from the Medical Research Council Laboratory of Molecular Biology in Cambridge report online February 14 in the Proceedings of the National Academy of Sciences. The team watched as misfolded clumps of the protein, called superoxide dismutase-1, made their way into nerve cells and induced normally harmless versions of the protein to clump up. These misfolded groups then popped out of the infected cell and into neighboring cells. This cycle is similar to how prions — the infectious proteins behind brain-wasting conditions such as Creutzfeldt-Jakob disease — spread through the brain. How the brain rewires
Nerve cells sprouting new connections are likely responsible for the brain’s ability to reroute sensory information after a serious spinal injury, an international team reports online February 16 in the Journal of Neuroscience. The results of the study, which was based on brain scans of volunteers with spinal injuries, runs counter to the theory that this job switch can be explained by the awakening of existing but dormant nerve cell connections.

News in Brief: Genes & Cells

Heritable sleep

Morning larks can thank their parents for their early waking habit. The team captured physical activity using monitors worn on the hip and used sleep diaries to learn the sleep habits of 723 Old Order Amish in Lancaster County, Penn. This insular population lives free from many sleep-confounding technological gadgets. On average, men work up at 4:59 a.m., while women slept in until about 5:14 a.m. Whether a subject rose early or late depended heavily on the waking habits of his or her relatives, researchers from the University of California, San Francisco and colleagues report in an upcoming Sleep.

Gene screens find incest

Genetic tests used to diagnose children with disabilities can also turn up evidence of incest. Assays designed to look for mutations also spot genome regions that contain far too little diversity, a sign that the parents are first-degree relatives. Several such cases have been identified already, scientists from Baylor College of Medicine in Houston report in the Feb. 12 Lancet. Finding incest can aid diagnosis and treatment of inherited disorders, since incest can lead to disabilities. But the information also raises thorny ethical issues, such as whether to report potential criminal conduct or to inform parents about what could be revealed before testing a child.

Flu changes

Some flu mutations go hand-in-hand, a new study finds. The results, appearing February 17 in PLoS Genetics, may help scientists predict what the next season’s flu will look like, enabling more effective vaccines. Researchers at the University of Pennsylvania in Philadelphia and colleagues scrutinized genetic changes for 40 years of different flu strains. Some of these mutations worked as a team, so that seeing one mutation increased the likelihood of the other one showing up in the next few years. The new technique was able to pick out several well-known mutations that confer Tamiflu resistance. The method may help researchers create consistently effective flu vaccines.

Gonorrhea got human DNA

Gonorrhea bacteria borrowed a piece of human DNA, researchers have discovered. Bacteria swap genetic material regularly, but it is rare for microbes to pick up DNA from their hosts. Seven of 62 strains of Neisseria gonorrhoeae studied contained a piece of human DNA known as an L1 element, a team at Northwestern University in Chicago reports online February 14 in the online journal mBio. Closely related species of Neisseria, including one that causes meningitis, do not have the human DNA, leading the researchers to speculate that gonorrhea bacteria picked up the L1 fragment relatively recently in evolutionary history.

Developmental difference

Mice are early bloomers, a study of the early development of mice and cattle reveals. Mice make the decision about which cells in the early embryo will form the placenta far earlier than cattle do, Debra Berg and colleagues at the AgResearch Crown Research Institute in Hamilton, New Zealand, report in the Feb. 15 Developmental Cell. Humans, pigs, rabbits and other mammals may follow the cattle’s timeline more closely than the mouse developmental clock, suggesting that cattle might be better animals to study than mice to understand the earliest stages of human development.


                                                                                                    V.JAHNAVI.

DNA EXTRACTION VEDIO.

Erythrocyte sedimentation rate

The erythrocyte sedimentation rate (ESR), also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour. It is a common hematology test that is a non-specific measure of inflammation. To perform the test, anticoagulated blood is placed in an upright tube, known as a Westergren tube, and the rate at which the red blood cells fall is measured and reported in mm/h.
Since the introduction of automated analyzers into the clinical laboratory, the ESR test has been automatically performed.

The ESR is governed by the balance between pro-sedimentation factors, mainly fibrinogen, and those factors resisting sedimentation, namely the negative charge of the erythrocytes (zeta potential). When an inflammatory process is present, the high proportion of fibrinogen in the blood causes red blood cells to stick to each other. The red cells form stacks called 'rouleaux,' which settle faster. Rouleaux formation can also occur in association with some lymphoproliferative disorders in which one or more immunoglobulin/s is/are secreted in high amounts. Rouleaux formation can, however, be a normal physiological finding in horses, cats, and pigs.

The ESR is increased by any cause or focus of inflammation. The ESR is increased in pregnancy or rheumatoid arthritis, and decreased in polycythemia, sickle cell anemia, hereditary spherocytosis, and congestive heart failure. The basal ESR is slightly higher in females.
History
This test was invented in 1897 by the Polish doctor Edmund Biernacki. In some parts of the world the test continues to be referred to as the Biernacki Test (Polish abbreviation: OB = Odczyn Biernackiego.) In 1918 the Swedish pathologist Robert Sanno Fåhræus declared the same and along with Alf Vilhelm Albertsson Westergren are eponymously remembered for the Fåhræus-Westergren test (abbreviated as FW test; in the UK, usually termed Westergren test), which uses sodium citrate-anticoagulated specimens.

Uses

Although it is frequently ordered, ESR is of limited use as a screening test in asymptomatic patients. It is useful for diagnosing diseases, such as multiple myeloma, temporal arteritis, polymyalgia rheumatica, various auto-immune diseases, systemic lupus erythematosus, rheumatoid arthritis, and chronic kidney diseases. In many of these cases, the ESR may exceed 100 mm/hour.

It is commonly used for a differential diagnosis for Kawasaki's disease and it may be increased in some chronic infective conditions like tuberculosis and infective endocarditis. It is a component of the PDCAI, an index for assessment of severity of inflammatory bowel disease in children.
The clinical usefulness of ESR is limited to monitoring the response to therapy in certain inflammatory diseases such as temporal arteritis, polymyalgia rheumatica and rheumatoid arthritis. It can also be used as a crude measure of response in Hodgkin's lymphoma. Additionally, ESR levels are used to define one of the several possible adverse prognostic factors in the staging of Hodgkin's lymphoma. There is also a wintrobe method.
The use of the ESR as a screening test in asymptomatic persons is limited by its low sensitivity and specificity. When there is a moderate suspicion of disease, the ESR may have some value as a "sickness index."
An elevated ESR in the absence of other findings should not trigger an extensive laboratory or radiographic evaluation.

Normal Values

Note: mm/hr. = millimeters per hour.

Westergren's original normal values (men 3mm and women 7mm) made no allowance for a person's age and in 1967 it was confirmed that ESR values tend to rise with age and to be generally higher in women. Values are increased in states of anemia, and in black populations.

Adults

The widely used rule for calculating normal maximum ESR values in adults (98% confidence limit) is given by a formula devised in 1983: ESR reference ranges from a large 1996 study with weaker confidence limits:

Age	20	55	90
Men	12	14	19
Women	18	21	23

Children

Normal values of ESR have been quoted as 1 to 2 mm/hr at birth, rising to 4 mm/hr 8 days after delivery,and then to 17 mm/hr by day 14.
Typical normal ranges quoted are:
 Newborn: 0 to 2 mm/hr

• Neonatal to puberty: 3 to 13 mm/hr, but other laboratories place an upper limit of 20.

Relation to C-reactive protein

C-reactive protein is an acute phase protein produced by the liver during an inflammatory reaction. Since C-reactive protein levels in the blood rise more quickly after the inflammatory or infective process begins, ESR is often replaced with C-reactive protein measurement. There are specific drawbacks, however, as they were found to be independently associated with a diagnosis of acute maxillary sinusitis so that the combination of the two measurements improved diagnostic sensitivity and specificity.

The Test

How is it used?

The erythrocyte sedimentation rate (ESR) is an easy, inexpensive, nonspecific test that has been used for many years to help detect conditions associated with acute and chronic inflammation, including infections, cancers, and autoimmune diseases. ESR is said to be nonspecific because increased results do not tell the doctor exactly where the inflammation is in the body or what is causing it, and also because it can be affected by other conditions besides inflammation. For this reason, the ESR is typically used in conjunction with other tests.

ESR is helpful in diagnosing two specific inflammatory diseases, temporal arteritis and polymyalgia rheumatica. A high ESR is one of the main test results used to support the diagnosis. It is also used to monitor disease activity and response to therapy in both of these diseases.

When is it ordered?

An ESR may be ordered when a condition or disease is suspected of causing inflammation somewhere in the body. There are numerous inflammatory conditions that may be detected using this test. For example, it may be ordered when arthritis is suspected of causing inflammation and pain in the joints or when digestive symptoms are suspected to be caused by inflammatory bowel disease.

A physician may order an ESR test (along with other tests) to evaluate a patient who has symptoms that suggest polymyalgia rheumatica or temporal arteritis, such as headaches, neck or shoulder pain, pelvic pain, anemia, unexplained weight loss, and joint stiffness. There are many other conditions that can result in a temporary or sustained elevation in the ESR.

Before doing an extensive workup looking for disease, a doctor may want to repeat the ESR test after a period of several weeks or months. If a doctor already knows the patient has a disease like temporal arteritis (where changes in the ESR mirror those in the disease process), she may order the ESR at regular intervals to assist in monitoring the course of the disease. In the case of Hodgkin's disease, for example, a sustained elevation in ESR may be a predictor of an early relapse following chemotherapy.

What does the test result mean?

Since ESR is a nonspecific marker of inflammation and is affected by other factors, the results must be used along with the doctor's other clinical findings, the patient's health history, and results from other appropriate laboratory tests. If the ESR and clinical findings match, the doctor may be able to confirm or rule out a suspected diagnosis. A single elevated ESR, without any symptoms of a specific disease, will usually not give the physician enough information to make a medical decision. Furthermore, a normal result does not rule out inflammation or disease.

Moderately elevated ESR occurs with inflammation, but also with anemia, infection, pregnancy, and old age.

A very high ESR usually has an obvious cause, such as a marked increase in globulins that can be due to a severe infection. The doctor will use other follow-up tests, such as blood cultures, depending on the patient's symptoms. People with multiple myeloma or Waldenstrom's macroglobulinemia (tumors that make large amounts of immunoglobulins) typically have very high ESRs even if they don't have inflammation. As noted before, those with polymyalgia rheumatica or temporal arteritis may also have very high ESRs.

A rising ESR can mean an increase in inflammation or a poor response to a therapy; a decreasing ESR can mean a good response.

Although a low ESR is not usually a cause for concern, it can be seen with conditions that inhibit the normal sedimentation of RBCs, such as polycythemia, extreme leukocytosis, and some protein abnormalities. Some changes in red cell shape (such as sickle cells in sickle cell anemia) also lower the ESR.

Is there anything else I should know?

ESR and C-reactive protein (CRP) are both markers of inflammation. Generally, ESR does not change as rapidly as does CRP, either at the start of inflammation or as it goes away. CRP is not affected by as many other factors as is ESR, making it a better marker of inflammation. However, because ESR is an easily performed test, many doctors still use ESR as an initial test when they think a patient has inflammation.

If the ESR is elevated, it is typically a result of globulins or fibrinogens. Your doctor may then order a fibrinogen level (a clotting protein that is another marker of inflammation) and a serum protein electrophoresis to determine which of these (or both) is causing the elevated ESR.

Females tend to have a higher ESR, and menstruation and pregnancy can cause temporary elevations.

In a pediatric setting, the ESR test is used for the diagnosis and monitoring of children with rheumatoid arthritis or Kawasaki disease.

Drugs such as dextran, methyldopa, oral contraceptives, penicillamine procainamide, theophylline, and vitamin A can increase ESR, while aspirin, cortisone, and quinine may decrease it.

There is a commercial rapid test available that performs the ESR in 4 minutes by a centrifugal method. It is being used more widely to shorten waiting times for patients, particularly in the Emergency Department.

1.  Should everyone have an ESR done?

The ESR is not a specific test — it does not point to any one condition or disease — and can be affected by many different factors other than inflammation. As such, it is not recommended for use in screening people without symptoms or apparently healthy people.

2.  What other tests might my doctor order besides ESR?

Your doctor may order the CRP test as well as other general tests, such as a comprehensive metabolic panel or a CBC, at the same time as the ESR. Your doctor may also order additional tests based on your symptoms, such as the ANA (antinuclear antibody) and RF (rheumatoid factor) tests for symptoms of arthritis, as well as a fibrinogen or serum protein electrophoresis.

3.  What do changes in my ESR mean?

The ESR may indicate the presence or abatement of infection or inflammation. If you have a chronic inflammatory disease, the ESR may fluctuate with the degree of activity of your condition.

                                                                                                                           V.jahnavi.

 Tuberculosis diagnosis

Tuberculosis is diagnosed by finding Mycobacterium tuberculosis bacteria in a clinical specimen taken from the patient. While other investigations may strongly suggest tuberculosis as the diagnosis, they cannot confirm it.

Diagnosis

A complete medical evaluation for tuberculosis (TB) must include a medical history, a physical examination, a chest X-ray and microbiological examination (of sputum or some other appropriate sample). It may also include a tuberculin skin test, other scans and X-rays, surgical biopsy.

Medical history

The medical history includes obtaining the symptoms of pulmonary TB: productive, prolonged cough of three or more weeks, chest pain, and hemoptysis. Systemic symptoms include low grade remittent fever, chills, night sweats, appetite loss, weight loss, easy fatiguability, and production of sputum that starts out mucoid but changes to purulent^[1]. Other parts of the medical history include prior TB exposure, infection or disease; past TB treatment; demographic risk factors for TB; and medical conditions that increase risk for TB disease such as HIV infection.
Tuberculosis should be suspected when a persistent respiratory illness in an otherwise healthy individual does not respond to regular antibiotics.

Physical examination

A physical examination is done to assess the patient's general health and find other factors which may affect the TB treatment plan. It cannot be used to confirm or rule out TB.

Microbiological studies

A definitive diagnosis of tuberculosis can only be made by culturing Mycobacterium tuberculosis organisms from a specimen taken from the patient (most often sputum, but may also include pus, CSF, biopsied tissue, etc.). A diagnosis made other than by culture may only be classified as "probable" or "presumed". For a diagnosis negating the possibility of tuberculosis infection, most protocols require that two separate cultures both test negative

Sputum

Sputum smears and cultures should be done for acid-fast bacilli if the patient is producing sputum^. The preferred method for this is fluorescence microscopy (auramine-rhodamine staining), which is more sensitive than conventional Ziehl-Neelsen staining. In cases where there is no spontaneous sputum production, a sample can be induced, usually by nebulized inhalation of a saline or saline with bronchodilator solution. A comparative study found that inducing three sputum samples is more sensitive than three gastric washings.

Alternative sampling

In patients incapable of producing a sputum sample, common alternative sample sources for diagnosing pulmonary tuberculosis include gastric washings, laryngeal swab, bronchoscopy (with bronchoalveolar lavage, bronchial washings, and/or transbronchial biopsy), and fine needle aspiration (transtracheal or transbronchial). In some cases, a more invasive technique is necessary, including tissue biopsy during mediastinoscopy or thoracoscopy.

PCR

Other mycobacteria are also acid-fast. If the smear is positive, PCR or gene probe tests can distinguish M. tuberculosis from other mycobacteria. Even if sputum smear is negative, tuberculosis must be considered and is only excluded after negative cultures.

Other

Many types of cultures are available . Traditionally, cultures have used the Löwenstein-Jensen (LJ), Kirchner, or Middlebrook media (7H9, 7H10, and 7H11). A culture of the AFB can distinguish the various forms of mycobacteria, although results from this may take four to eight weeks for a conclusive answer. New automated systems that are faster include the MB/BacT, BACTEC 9000, and the Mycobacterial Growth Indicator Tube (MGIT). The Microscopic Observation Drug Susceptibility assay culture may be a faster and more accurate method

Radiography

Chest X-ray

Tuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe.

In active pulmonary TB, infiltrates or consolidations and/or cavities are often seen in the upper lungs with or without mediastinal or hilar lymphadenopathy or pleural effusions ( tuberculous pleurisy). However, lesions may appear anywhere in the lungs. In disseminated TB a pattern of many tiny nodules throughout the lung fields is common - the so called miliary TB. In HIV and other immunosuppressed persons, any abnormality may indicate TB or the chest X-ray may even appear entirely normal.
Abnormalities on chest radiographs may be suggestive of, but are never diagnostic of, TB. However, chest radiographs may be used to rule out the possibility of pulmonary TB in a person who has a positive reaction to the tuberculin skin test and no symptoms of disease.

Cavitation or consolidation of the apexes of the upper lobes of the lung may be discernible by a chest x-ray

Abreugraphy

A variant of the chest X-Ray, abreugraphy (from the name of its inventor, Dr. Manuel Dias de Abreu) was a small radiographic image, also called miniature mass radiography (MMR) or miniature chest radiograph. Though its resolution is limited (it doesn't allow the diagnosis of lung cancer, for example) it is sufficiently accurate for diagnosis of tuberculosis.
Much less expensive than traditional X-Ray, MMR was quickly adopted and extensively utilized in some countries, in the 1950s. For example, in Brazil and in Japan, tuberculosis prevention laws went into effect, obligating ca. 60% of the population to undergo MMR screening.
The procedure went out of favor, as the incidence of tuberculosis dramatically decreased, but is still used in certain situations, such as the screening of prisoners and immigration applicants..

Tuberculin skin test (TST)

Two tests are available: the Mantoux and Heaf tests.

Mantoux skin test

The Mantoux test for TB involves intradermally injecting PPD (Purified Protein Derivative) tuberculin and measuring the size of induration 48-72 hours later.

The Mantoux skin test is used in the United States and is endorsed by the American Thoracic Society and Centers for Disease Control and Prevention (CDC).

If a person has had a history of a positive tuberculin skin test, another skin test is not needed.

Heaf test

For more details on this topic, see Heaf test.

The Heaf test was used in the United Kingdom until 2005, and is graded on a four point scale. The Mantoux test is now used.
The equivalent Mantoux test positive levels done with 10 TU (0.1 ml 100 TU/ml, 1:1000) are

• 0–4 mm induration (Heaf 0 to 1)
• 5–14 mm induration (Heaf 2)
• Greater than 15 mm induration (Heaf 3 to 5)

CDC classification of tuberculin reaction

An induration (palpable raised hardened area of skin) of more than 5–15 mm (depending upon the person's risk factors) to 10 Mantoux units is considered a positive result, indicating TB infection.

• 5 mm or more is positive in
• HIV-positive person
• Recent contacts of TB case
• Persons with nodular or fibrotic changes on CXR consistent with old healed TB
• Patients with organ transplants and other immunosuppressed patients

• 10 mm or more is positive in
• Recent arrivals (less than 5 years) from high-prevalent countries
• Injection drug users
• Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters, etc.)
• Mycobacteriology lab personnel
• Persons with clinical conditions that place them at high risk (e.g., diabetes, prolonged corticosteroid therapy, leukemia, end-stage renal disease, chronic malabsorption syndromes, low body weight, etc)
• Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories

• 15 mm or more is positive in
• Persons with no known risk factors for TB
• (Note: Targeted skin testing programs should only be conducted among high-risk groups)

A tuberculin test conversion is defined as an increase of 10 mm or more within a 2-year period, regardless of age.

BCG vaccine and tuberculin skin test

There is disagreement on the use of the Mantoux test on people who have been immunized with BCG. The US recommendation is that in administering and interpreting the Mantoux test, previous BCG vaccination should be ignored; the UK recommendation is that interferon-γ tests should be used to help interpret positive tuberculin tests, also, the UK do not recommend serial tuberculin skin testing in people who have had BCG (a key part of the US strategy). In their guidelines on the use of QuantiFERON Gold the US Centers for Disease Control and Prevention state that whereas Quantiferon Gold is not affected by BCG inoculation tuberculin tests can be affected. In general the US approach is likely to result in more false positives and more unnecessary treatment with potentially toxic drugs; the UK approach is as sensitive in theory and should also be more specific, because of the use of interferon-γ tests.
Under the US recommendations, diagnosis and treatment of latent tuberculosis infection (LTBI) is considered for any BCG-vaccinated person whose skin test is 10 mm or greater, if any of these circumstances are present:

• Was in contact with another person with infectious TB
• Was born or has resided in a high TB prevalence country
• Is continually exposed to populations where TB prevalence is high.

Laboratory

Because of difficulties with the Tuberculin skin test, many laboratory methods of diagnosis are emerging. These tests have been reviewed in detail

Adenosine deaminase

In 2007, a systematic review of adenosine deaminase by the NHS Health Technology Assessment Programme concluded "There is no evidence to support the use of ADA tests for the diagnosis of pulmonary TB. However, there is considerable evidence to support their use in pleural fluid samples for diagnosis of pleural TB, where sensitivity was very high, and to a slightly lesser extent for TB meningitis. In both pleural TB and TB meningitis, ADA tests had higher sensitivity than any other tests."

Nucleic acid amplification tests (NAAT)

This is a heterogeneous group of tests that use the polymerase chain reaction (PCR) technique to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor (Roche Diagnostics). In 2007, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that "NAAT test accuracy to be far superior when applied to respiratory samples as opposed to other specimens. Although the results were not statistically significant, the AMTD test appears to perform better than other currently available commercial tests." In a more recent before-after observational study, found that use of the MTD test reduce inappropriate tuberculosis therapy. The study found the accuracy of the MTD test as follows: Overall

• sensitivity 92%
• specificity 99%

Smear positive patients

• sensitivity 99%
• specificity 98%

Smear negative patients

• sensitivity 62%
• specificity 99%

Full blood count

Although a full blood count is never diagnostic, normocytic anemia and lymphopenia are common. Neutrophilia is rarely found. [iron deficiency anemia may develop with isoniazid treatment] Urea and electrolytes are usually normal, although hypocalcemia and hyponatremia are possible in tuberculous meningoencephalitis due to SIADH. In advanced disease, hypoalbuminemia, hyperproteinemia, and hyperglobulinemia may be present.^[9]
Erythrocyte sedimentation rate is usually raised.

Interferon-γ release assays

Interferon-γ (interferon-gamma) release assays (IGRAs) are exciting new developments in TB infection testing. IGRAs are based on the ability of the Mycobacterium tuberculosis antigens for early secretory antigen target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) to stimulate host production of interferon-gamma. Because these antigens are not present in non-tuberculous mycobacteria or in any BCG vaccine variant, these tests can distinguish latent tuberculosis infection (LTBI).
The blood tests QuantiFERON-TB Gold In Tube and T-SPOT.TB use these antigens to detect people with tuberculosis. Lymphocytes from the patient's blood are incubated with the antigens. These tests are called interferon γ tests and are not equivalent. If the patient has been exposed to tuberculosis before, T lymphocytes produce interferon γ in response. The QuantiFERON-TB Gold In Tube uses an ELISA format to detect the whole blood production of interferon γ with great sensitivity (89%). The distinction between the tests is that QuantiFERON-TB Gold quantifies the total amount of interferon γ when whole blood is exposed to the antigens(ESAT-6,CFP-10 and TB 7.7(p4)), whereas Guidelines for the use of the FDA approved QuantiFERON-TB Gold were released by the CDC in December 2005. In October 2007, the FDA gave approval of QuantiFERON-TB Gold In Tube for use in the United States.
The enzyme-linked immunospot assay (ELISPOT) is another blood test available in the UK that may replace the skin test for diagnosis ^{[11] [12] [13]}. T-SPOT.TB, a type of ELISPOT assay,^]counts the number of activated T lymphocytes that secrete interferon γ.
For diagnosing latent TB, three systematic reviews of IGRAs concluded the tests noted excellent specificity for the tests to distinguish latent TB from prior vaccination. According to a study from Korea, where there is a high prevalence of LTBI, QuantiFERON-TB Gold and T-SPOT.TB have good sensitivity but reduced specificity for diagnosing active TB, due to their ability to detect latent TB. In a recently published metaanalysis, with data from both developed and developing countries, QuantiFERON-TB Gold In Tube had a pooled sensitivity for active TB of 81% and specificity of 99.2%, whereas T-SPOT.TB had a pooled sensitivity of 87.5% and specificity of 86.3%. In head-to-head comparisons, the sensitivity of IGRAs surpassed TST. The authors concluded that IGRAs are "superior to the TST for detecting confirmed active TB disease

Public health

When someone is diagnosed with tuberculosis, all their close contacts should be screened for TB with a tuberculin skin test or a chest x-ray or both.

Tuberculosis classification system used in the US

The current clinical classification system for TB (Class 0 to 5) is based on the pathogenesis of the disease.
The U.S. Citizenship and Immigration Services has an additional TB classification (Class A, B1, or B2) for immigrants and refugees developed by the Centers for Disease Control and Prevention (CDC). The (Class) B notification program is an important screening strategy to identify new arrivals who have a high risk for TB.