This article needs to be updated.(May 2020) |
This article contains a lot of positive statements with no indication that most of them apply to all automated real-time PCR tests, not just this proprietary brand (see Cepheid (company)). The difference between a GeneXpert MTB/RIF test and a GeneXprt test for anything else is swapping out a single reagent, so it would be repetitive to have a separate article for each one (see Cepheid (company)#System). The omission of this context means that it contains content that is written like an advertisement .(May 2022) |
The Xpert MTB/RIF is a cartridge-based nucleic acid amplification test (NAAT) for simultaneous rapid tuberculosis diagnosis and rapid antibiotic sensitivity test. It is an automated diagnostic test that can identify Mycobacterium tuberculosis (MTB) DNA and resistance to rifampicin (RIF). It was co-developed by the laboratory of Professor David Alland at the University of Medicine and Dentistry of New Jersey (UMDNJ), [1] Cepheid Inc. and Foundation for Innovative New Diagnostics, with additional financial support from the US National Institutes of Health (NIH). [2]
In December 2010, the World Health Organization (WHO) endorsed the Xpert MTB/RIF for use in tuberculosis (TB) endemic countries. [3] The announcement followed 18 months of assessing its field effectiveness in TB, MDR-TB, and TB/HIV co-infection. [4] The test may enable the diagnosis of TB in patients likely to be missed by traditional tests. [4] [5]
According to the Centers for Disease Control and Prevention (CDC) in 2015, [6] the Xpert MTB/RIF test was "revolutionizing TB control by contributing to the rapid diagnosis of TB disease and drug resistance. The test simultaneously detects Mycobacterium tuberculosis complex (MTBC) and resistance to rifampin (RIF) in less than 2 hours. In comparison, standard cultures can take 2 to 6 weeks for MTBC to grow and conventional drug resistance tests can add 3 more weeks." [6]
The Xpert MTB/RIF detects DNA sequences specific for Mycobacterium tuberculosis and rifampicin resistance by polymerase chain reaction. [5] [7] It is based on the Cepheid GeneXpert system, a rapid, simple-to-use nucleic acid amplification test (NAAT). The Xpert® MTB/RIF purifies and concentrates Mycobacterium tuberculosis bacilli from sputum samples, isolates genomic material from the captured bacteria by sonication and subsequently amplifies the genomic DNA by PCR. The process identifies most of the clinically relevant Rifampicin resistance inducing mutations in the RNA polymerase beta (rpoB) gene in the Mycobacterium tuberculosis genome in a real time format using fluorescent probes called molecular beacons. Results are obtained from unprocessed sputum samples in 90 minutes, with minimal biohazard and very little technical training required to operate. [8] This test was developed as an on-demand near patient technology which could be performed even in a doctor's office if necessary.
A review to assess the diagnostic accuracy of Xpert TB found that when used as an initial test to replace smear microscopy it had pooled sensitivity of 89% and specificity of 99% . However, when Xpert TB was used as an add-on for cases of negative smear microscopy the sensitivity was only 67% and specificity 99%. [9] In a clinical study conducted the sensitivity of the MTB/RIF test on just 1 sputum sample was 92.2% for culture-positive TB; 98.2% for smear+ and culture-positive cases; and 72.5% for smear-negative, culture-positive cases, with a specificity of 99.2%. Sensitivity and higher specificity were slightly higher when 3 samples were tested. [10]
Some concerns have been raised about the Xpert MTB/RIF, including minor operational issues and cost. The concessional price for a GeneXpert system is currently 32,000 USD for a four module instrument. As of 6 August 2012, the cost of a test cartridge in countries eligible for concessional pricing is $9.98 USD. [11] [12] [13] As of 30 June 2013, 1,402 GeneXpert systems (comprising 7553 modules) and >3 million Xpert MTB/RIF cartridges had been procured in 88 of the 145 countries under concessional pricing. [14]
In August 2020, Vietnam Ministry of Health had approved the use of GeneXpert, that has been used in Vietnam tuberculosis prevention network since 2012, for COVID-19 testing. According to Nguyen Viet Nhung, director of the National Lung Hospital in Hanoi, the test is similar to RT-PCR, gives accurate results within 35–45 minutes for both COVID-19 and tuberculosis, and could work automatically. [15] It is also used for COVID-19 testing at six sites across Somalia. [16] GeneXpert is rapid test for COVID-19 with processing time of around 45 mins and less cost. [17]
Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. Infection of other organs can cause a wide range of symptoms.
Mycobacterium tuberculosis, also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface primarily due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, and as a result, M. tuberculosis can appear weakly Gram-positive. Acid-fast stains such as Ziehl–Neelsen, or fluorescent stains such as auramine are used instead to identify M. tuberculosis with a microscope. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, it infects the lungs. The most frequently used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain, culture, and polymerase chain reaction.
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis rifamycinica or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections.
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), Mycobacterium avium complex, leprosy, and Legionnaires' disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.
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.
Tuberculosis management describes the techniques and procedures utilized for treating tuberculosis (TB) or simply a treatment plan for TB.
Antibiotic sensitivity testing or antibiotic susceptibility testing is the measurement of the susceptibility of bacteria to antibiotics. It is used because bacteria may have resistance to some antibiotics. Sensitivity testing results can allow a clinician to change the choice of antibiotics from empiric therapy, which is when an antibiotic is selected based on clinical suspicion about the site of an infection and common causative bacteria, to directed therapy, in which the choice of antibiotic is based on knowledge of the organism and its sensitivities.
The rpoB gene encodes the β subunit of bacterial RNA polymerase and the homologous plastid-encoded RNA polymerase (PEP). It codes for 1342 amino acids in E. coli, making it the second-largest polypeptide in the bacterial cell. It is targeted by the rifamycin family of antibacterials, such as rifampin. Mutations in rpoB that confer resistance to rifamycins do so by altering the protein's drug-binding residues, thereby reducing affinity for these antibiotics.
Tuberculous meningitis, also known as TB meningitis or tubercular meningitis, is a specific type of bacterial meningitis caused by the Mycobacterium tuberculosis infection of the meninges—the system of membranes which envelop the central nervous system.
Lipoarabinomannan, also called LAM, is a glycolipid, and a virulence factor associated with Mycobacterium tuberculosis, the bacteria responsible for tuberculosis. Its primary function is to inactivate macrophages and scavenge oxidative radicals.
Extensively drug-resistant tuberculosis (XDR-TB) is a form of tuberculosis caused by bacteria that are resistant to some of the most effective anti-TB drugs. XDR-TB strains have arisen after the mismanagement of individuals with multidrug-resistant TB (MDR-TB).
Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs): isoniazid and rifampicin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).
The National Tuberculosis Elimination Programme (NTEP), earlier known as the Revised National Tuberculosis Control Programme (RNTCP), is the Public Health initiative of the Government of India that organizes its anti-Tuberculosis efforts. It functions as a flagship component of the National Health Mission (NHM) and provides technical and managerial leadership to anti-tuberculosis activities in the country. As per the National Strategic Plan 2017–25, the program has a vision of achieving a "TB free India",with a strategies under the broad themes of "Prevent, Detect,Treat and Build pillars for universal coverage and social protection". The program provides, various free of cost, quality tuberculosis diagnosis and treatment services across the country through the government health system.
Löwenstein–Jensen medium, more commonly known as LJ medium, is a growth medium specially used for culture of Mycobacterium species, notably Mycobacterium tuberculosis.
FIND is a global health non-profit based in Geneva, Switzerland. FIND functions as a product development partnership, engaging in active collaboration with over 150 partners to facilitate the development, evaluation, and implementation of diagnostic tests for poverty-related diseases. The organisation's Geneva headquarters are in Campus Biotech. Country offices are located in New Delhi, India; Cape Town, South Africa; and Hanoi, Viet Nam.
Tuberculous pericarditis is a form of pericarditis. It is a condition in which the pericardium surrounding the heart is infected by the bacterial species Mycobacterium tuberculosis. Tuberculous pericarditis accounts for a significant percentage of presentations of tuberculosis worldwide. The condition has four stages of disease which manifests with clinical presentations ranging from acute pericarditis to overt heart failure. Tuberculous pericarditis is an under-diagnosed condition. Diagnosis often requires a range of diagnostic tools, including pericardiocentesis, biochemical tests, and imaging. Treatment of this disease is similar to treatment of pulmonary tuberculosis. Alternative treatment options to reduce cardiac complications are also available.
Cepheid is an American molecular diagnostics company that is a wholly owned subsidiary of Danaher Corporation. Its systems automate traditional nucleic acid tests. The tests can be used to identify and analyze pathogens and genetic disorders. Cepheid sells clinical tests for healthcare-associated infections, infectious diseases, sexual health, oncology and genetics.
Keertan Dheda MBBCh (Wits), FCP(SA), FCCP, PhD (Lond), FRCP (Lond), born in 1969, is a Professor of Mycobacteriology and Global health at the London School of Hygiene and Tropical Medicine (LSHTM) with an extra-mural joint appointment at the University of Cape Town (UCT), where he is a Professor of Respiratory Medicine.
Truenat is a chip-based, point-of-care, rapid molecular test for diagnosis of infectious diseases. The technology is based on the Taqman RTPCR chemistry which can be performed on the portable, battery operated Truelab Real Time micro PCR platform. Truenat is developed and manufactured by Goa-based Molbio Diagnostics Private Limited.
Catharina Boehme is the Assistant Director-General for External Relations and Governance of the World Health Organization. She previously served as WHO Chef de Cabinet, and is known for her work in developing diagnostic tests for diseases such as tuberculosis and for advocating for increased testing for the COVID-19 disease.