DNA fingerprinting of Mycobacterium tuberculosis: lessons learned and implications for the future. (Tuberculosis Genotyping Network).DNA fingerprinting DNA fingerprinting or DNA profiling, any of several similar techniques for analyzing and comparing DNA from separate sources, used especially in law enforcement to identify suspects from hair, blood, semen, or other biological materials found at of Mycobacterium mycobacterium
Any of the rod-shaped bacteria that make up the genus Mycobacterium. The two most important species cause tuberculosis and leprosy in humans; another species causes tuberculosis in both cattle and humans. tuberculosis--a relatively new laboratory technique--offers promise as a powerful aid in the prevention and control of tuberculosis (TB). Established in 1996 by the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (CDC See Control Data, century date change and Back Orifice.
CDC - Control Data Corporation ), the National Tuberculosis Genotyping Genotyping refers to the process of determining the genotype of an individual with a biological assay. Current methods of doing this include PCR, DNA sequencing, and hybridization to DNA microarrays or beads. and Surveillance Network was a 5-year prospective, population-based study of DNA fingerprinting conducted from 1996 to 2000. The data from this study suggest multiple molecular epidemiologic and program management uses for DNA fingerprinting in TB public health practice. From these data, we also gain a clearer understanding of the overall diversity of M. tuberculosis M. tuberculosis,
n the bacterium responsible for tuberculosis, generally a respiratory infection in man; nonrespiratory tuberculosis is considered an indicator disease for AIDS. See also tuberculosis. strains as well as the presence of endemic strains in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. . We summarize the key findings and the impact that DNA fingerprinting may have on future approaches to TB control. Although challenges and limitations to the use of DNA fingerprinting exist, the widespread implementation of the technique into routine TB prevention and control practices appears scientifically justified.
The capacity to differentiate Mycobacterium tuberculosis Mycobacterium tuberculosis
Mycobacterium tuberculosis strain patterns by DNA fingerprinting has shown promise in tuberculosis (TB) control since this tool was first applied to outbreak investigations (1-3) and population-based studies (4,5) in the early 1990s. Evaluating this tool and determining its limitations are important activities in view of the most recent efforts to eliminate TB in the United States after its resurgence in the early 1990s (6). In 1996, the Centers for Disease Control and Prevention (CDC) initiated a 5-year, prospective, population-based study, the National Tuberculosis Genotyping and Surveillance Network. Most findings represented in this issue of Emerging Infectious Diseases An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and threatens to increase in the near future. EIDs include diseases caused by a newly identified microorganism or newly identified strain of a known microorganism (e.g. come from this study. In this synopsis, we address two important implications for DNA fingerprinting of M. tuberculosis: its varied utility as a tool in TB prevention and control and its value in the measurement of the overall diversity of M. tuberculosis strain patterns in the United States, including differences by region and population and the prevalence of endemic strains.
Identification of Laboratory Cross-Contamination or Mislabeling mislabeling,
n 1. the inaccurate identification of a product in which the label lists ingredients or components that are not actually included within the product.
DNA fingerprinting of M. tuberculosis has been shown to identify and confirm laboratory cross-contamination or mislabeling. Previous retrospective studies retrospective study,
a study in which a search is made for a relationship between one phenomenon or condition and another that occurred in the past (e.g. describing M. tuberculosis laboratory cross-contamination or mislabeling found rates between 0.9% and 3.5% (7-14). In this issue, Northrup et al. (15) report a rate of 1.5%, which is within the range of published rates. Therefore, of 13,035 culture-positive TB casepatients reported in the United States in 2000, TB may have been misdiagnosed in as many as 117 (0.9%) to 456 (3.5%) persons. Using the previously reported finding that two thirds of case-patients with false-positive cultures are treated (11), we estimate that 78-304 persons may have been misdiagnosed and treated unnecessarily in the United States in 2000.
To measure the direct and indirect financial costs associated with these laboratory cross-contamination or mislabeling events, Northrup et al. (15) discuss data about three persons who were falsely diagnosed as having TB. In 1999 U.S. dollars, the estimated average cost to the health-care system for each person was $32,231 and the estimated average direct cost for each person was $10,744; thus, the estimated average cost for misdiagnosis mis·di·ag·no·sis
n. pl. mis·di·ag·no·ses
An incorrect diagnosis.
mis·diag·nose of TB was $42,975 per person. This study did not include indirect and intangible costs, which can be substantial and are largely paid by the patient. Therefore, these costs are underestimates of the true costs associated with these events. Extrapolating these cost estimates to the national level and assuming that 78-304 persons were misdiagnosed and treated in 2000, we estimate that the preventable costs to the U.S. health-care system were $3.35 million to $13.06 million in 2000.
To examine the potential to predict laboratory cross-contamination or mislabeling, Jasmer et al. (16) established reproducible and predetermined pre·de·ter·mine
v. pre·de·ter·mined, pre·de·ter·min·ing, pre·de·ter·mines
1. To determine, decide, or establish in advance: criteria on the basis of DNA fingerprinting. They prospectively reviewed these events in three large, experienced laboratories in California. Laboratory procedures were reviewed at the start of the study; culture-positive results for 6 (2%) of 296 persons were caused by laboratory cross-contamination, which could be identified a priori a priori
In epistemology, knowledge that is independent of all particular experiences, as opposed to a posteriori (or empirical) knowledge, which derives from experience. . In this study, five of the six persons received unnecessary, expensive, and potentially dangerous medical treatment.
Monitoring Interjurisdictional Transmission
The impact of epidemic spread of TB across state or jurisdictional boundaries and the necessity for interjurisdictional public health collaboration are not always fully accepted or appreciated, due in large part to the constitutionally mandated independence of state governments for public health practice. Many reports of localized-only epidemic transmission (17) suggest that most transmission of TB in the United States occurs locally. Indeed, Ellis et al. (18) show that most clusters (66% or 680/1,029) from the National Tuberculosis Genotyping and Surveillance Network were restricted to a single site.
However, a few recent reports illustrate the importance of the wider geographic spread of TB and the necessity for interjurisdictional collaboration (19,20). Ellis et al. also show that 260 (25%) clusters from the genotyping surveillance network were found in two sites, 55 (5%) in three, 19 (2%) in four, 8 (1%) in five, and 7 (1%) in six sites. As expected, clusters that multiple sites included more case-patients. Maximum cluster size and absolute numbers of case-patients with isolates that clustered continued to increase through the end of the study. Though many of the case-patients in clusters that spanned these multiple sites may not be epidemiologically linked, other examples of interjurisdictional transmission exist (19-22).
We know that TB is problematic in certain groups at high risk (i.e., homeless persons An individual who lacks housing, including one whose primary residence during the night is a supervised public or private facility that provides temporary living accommodations; an individual who is a resident in transitional housing; or an individual who has as a primary residence a ) (23-29). With this in mind, an exception to the concept of local-only spread is described by Lathan et al. (30). They present data showing that interjurisdictional collaboration in TB control was necessary to control epidemic spread between adjacent jurisdictions (i.e., Maryland with Washington D.C.). Through combined DNA fingerprinting cluster analyses, these researchers found additional and unsuspected TB transmission that not only crossed state lines but also crossed social lines (i.e., between homeless and non-homeless persons).
McElroy et al. (31) show the value of a system to compare DNA fingerprinting data across jurisdictions, especially during multistate mul·ti·state
Of, relating to, or involving several states: a multistate environmental campaign. TB outbreak settings. Facilitating an interjuridictional investigation of TB first recognized in Maryland, they extended the investigation outside of Maryland and discovered an additional 18 case-patients linked to the original 21 previously described.
TB control programs that employ DNA fingerprinting should work with neighboring neigh·bor
1. One who lives near or next to another.
2. A person, place, or thing adjacent to or located near another.
3. A fellow human.
4. Used as a form of familiar address.
v. jurisdictions to devise strategies that promote rapid sharing of results. Comprehensive interjurisdictional monitoring of transmission would require a national registry of DNA fingerprinting data and a system to alert public health officials about interjurisdictional clustering.
Program Evaluation Program evaluation is a formalized approach to studying and assessing projects, policies and program and determining if they 'work'. Program evaluation is used in government and the private sector and it's taught in numerous universities.
Understanding the transmission characteristics of multidrug-resistant TB strains is essential for developing successful control strategies. Multidrug-resistant TB is an important problem and represents a life-threatening condition; patients often require prolonged treatment and frequent hospitalization hospitalization /hos·pi·tal·iza·tion/ (hos?pi-t'l-i-za´shun)
1. the placing of a patient in a hospital for treatment.
2. the term of confinement in a hospital. . The potentially serious side effects Side effects
Effects of a proposed project on other parts of the firm. of second-line TB drugs challenge effective treatment and the resources of the patient and the health-care system (32).
One indicator for the success of a TB control program's performance is a decline in TB incidence rate over time. Incident TB case-patients include those recently infected who progress rapidly to active TB and those with remote infection who progress after years of latency and are later diagnosed with active TB. However, in high transmission circumstances, recent disease transmission likely accounts for most incident TB case-patients. DNA fingerprinting clustering may reflect recent TB transmission (4,5,33,34), albeit with methodological and population characteristic caveats (35-37). Therefore, the decline in the incidence of clustering can indicate the impact of interventions aimed at reducing recent TB transmission (38).
Munsiff et al. (39) describe how DNA fingerprinting, specifically molecular clustering of multidrug-resistant TB strains as a surrogate surrogate n. 1) a person acting on behalf of another or a substitute, including a woman who gives birth to a baby of a mother who is unable to carry the child. 2) a judge in some states (notably New York) responsible only for probates, estates, and adoptions. of recent transmission, was used to monitor an improved TB program in New York City New York City: see New York, city.
New York City
City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S. . During a 3-year period (1995-1997), multidrug-resistant TB was diagnosed for 241 case-patients (4.9% of all culture-positive, TB case-patients) in New York City. These 241 case-patients were more likely than culture-positive, non-multidrug-resistant TB case-patients to have been born in the United States, to be infected with HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. , to be health-care workers, and to have positive acid-fast bacilli bacilli /ba·cil·li/ (bah-sil´i) plural of bacillus.
see bacillus. smear results. During this study period, of 234 multidrug-resistant TB case-patients with DNA fingerprinting results, 153 (65%) were grouped into 19 clusters. Epidemiologic links were identified for 25 (19.8%) case-patients clustered by DNA fingerprinting.
Kong et al. from Denver (40) demonstrate the role of DNA fingerprinting to measure the performance of a tuberculin tuberculin /tu·ber·cu·lin/ (-lin) a sterile solution containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis; see also under test. skin-test program among homeless persons. They showed a decrease in clustering (a surrogate of recent TB transmission) from 49% during the 7-year period before the program was implemented to 14% in the 4-year period after the program. This assessment is a logical extension of the usefulness of DNA fingerprinting technology, since a previous report from Denver by Burman et al. (41) showed that homelessness was a predictor of DNA fingerprint DNA fingerprint
An individual's unique sequence of DNA base pairs. Also called genetic fingerprint. clustering.
Ellis et al. (18) show that, despite a decrease in TB incidence rates at all genotyping surveillance network sites, the proportion of cases in clusters stabilized at a relatively high level (~48%). They suggest that this high proportion of clustering may be due to the inclusion of many low-incidence, stable populations in which persons in chains of transmission from past decades still reside in proximity (42). Alternative explanations include a slightly younger population under study, the presence of old endemic strains that have spread widely, and the limited discrimination of low-copy number IS6110 restriction fragment length polymorphism restriction fragment length polymorphism
n. Abbr. RFLP
Intraspecies variations in the length of DNA fragments generated by the action of restriction enzymes and caused by mutations that alter the sites at which these enzymes act, changing (RFLP RFLP
restriction fragment length polymorphism
restriction fragment length polymorphism.
RFLP ) patterns, even with the addition of spoligotyping as a secondary test. Although the overall proportion of case-patients in clusters plateaued at approximately 48% over the 5 years of study, the annualized annualized
Of or relating to a variable that has been mathematically converted to a yearly rate. Inflation and interest rates are generally annualized since it is on this basis that these two variables are ordinarily stated and compared. proportion of case-patients in clusters decreased over time with a concomitant decrease in TB incidence. This finding, which might reflect more effective TB control in limiting ongoing transmission, is provocative and merits further investigation.
Statewide Assessment of Circumstances and Settings for TB Transmission
The statewide use of DNA fingerprinting provides an informed picture of the epidemiologic features of disease transmission (36-38). Cronin et al. (43) describe a specific example in Maryland. During a 5-year period, they used DNA fingerprinting on >99% of all isolates in the state and found that cluster investigations were very effective in identifying additional epidemiologic links, many of which occurred in nontraditional settings. Specifically, isolates from 436 (37%) of 1,172 Maryland case-patients were clustered by DNA fingerprinting. Of those 436 clustered case-patients, these researchers found 155 (36%) to be epidemiologically linked using traditional contact investigation.
Miller et al. (44) provide another example of statewide use of DNA fingerprinting by exploring the impact of DNA fingerprinting used in Massachusetts during investigations of a TB outbreak and a laboratory cross-contamination event. These researchers also describe how DNA fingerprinting affected the identification of M. tuberculosis strains and transmission sites and accurate epidemiologic links. Overall, they found that, in addition to 129 epidemiologic relationships found before DNA fingerprinting results were obtained, 12 other epidemiologic relationships involving 20 persons were discovered as a result of cluster investigations. In addition, they determined places of transmission previously unrecognized and used DNA fingerprinting to refute re·fute
tr.v. re·fut·ed, re·fut·ing, re·futes
1. To prove to be false or erroneous; overthrow by argument or proof: refute testimony.
2. a purported TB outbreak.
Sharnprapai et al. (45) also report on the use of DNA fingerprinting to further understand the epidemiology and transmission patterns of TB in Massachusetts. In this study, 28% of TB case-patients were clustered, and case-patients born in the United States were two times more likely to cluster than case-patients not born in the United States. Furthermore, they point out a very important limitation to interpreting and using DNA fingerprinting data. Despite using a secondary typing method (spoligotyping) with strains that have six or fewer copies of IS6110, a limited ability to differentiate these strains exists. In their study, clusters of strains with more than six copies of IS6110 were more likely to have epidemiologic links found than clusters of strains with six or fewer copies of IS6110. The report by Dillaha et al. (46) describes the subtleties of disease transmission faced by TB programs in low-incidence states (specifically Arkansas), which are in the forefront as the United States moves toward TB elimination. Thirty-five case-patients in a 54-year period with identical or very similar fingerprints Impressions or reproductions of the distinctive pattern of lines and grooves on the skin of human fingertips.
Fingerprints are reproduced by pressing a person's fingertips into ink and then onto a piece of paper. were identified. After reviewing the endemic strain, these researchers recognized the lack of success with traditional contact tracing In epidemiology, contact tracing is the identification and diagnosis of persons who may have come into contact with an infected person. For sexually transmitted diseases, this is generally limited to sexual partners but for highly virulent diseases such as Ebola and tuberculosis, a and treatment recommendations for latent TB infection for persons with positive tuberculin skin tests Tuberculin Skin Test Definition
Tuberculosis (TB) is an airborne infectious disease caused by the bacteria Mycobacterium tuberculosis. Besides culturing in the laboratory, the two most common types of tests to screen for exposure to this disease . This critical determination has implications for other low-incidence areas. In addition to the traditional focus on personal contacts, Dillaha et al. recommend case finding and screening on the basis of geographic location. With the advent of geographic interface technology and mapping, this new public health strategy might be feasible. Additionally, these findings support the usefulness of a social network approach to contact investigation.
The value of DNA fingerprinting has been shown clearly during outbreak investigations (1-3). During every investigation, one overriding question recurs: which case-patients related to the outbreak are part of the chain of transmission and are not unrelated, sporadic cases? DNA fingerprinting can help researchers determine whether patients are related to the outbreak and thus focus the epidemiologic investigation.
An intriguing new benefit of coupling DNA fingerprint information with outbreak investigation lies in the power of this tool to increase understanding of the often difficult to discern transmission patterns of community TB disease (47) and uncover previously unknown outbreaks. Ijaz et al. (48) show this potential use by demonstrating that molecular clusters could show previously unsuspected instances of probable TB transmission, prompting more directed investigations to seek epidemiologic links missed by routine contact investigation. In the study, cluster analysis Cluster analysis
A statistical technique that identifies clusters of stocks whose returns are highly correlated within each cluster and relatively uncorrelated across clusters. Cluster analysis has identified groupings such as growth, cyclical, stable, and energy stocks. was based on identical and similar DNA fingerprinting patterns, broadening the group of patients included in the initial analysis.
In their study, secondary typing was accomplished by using a polymorphic polymorphic - polymorphism GC-rich sequence for identical IS6110based DNA fingerprinting patterns with six or fewer bands or for patterns with more than six bands that were similar but differed by a single band (49). In further investigations of clusters with this "broader net," among 66% of case-patients, Ijaz et al. uncovered additional epidemiologic links missed during routine contact investigations in Arkansas. During this process, they found an extensive, previously unknown social network that aided public health investigations. Ijaz et al; conclude that. patients whose isolates have similar but not identical IS6110 patterns should be considered potential members of a cluster and be included during epidemiologic investigations.
Oh et al. (50) help establish the value of DNA fingerprinting in an unusual outbreak setting, a zoo. They describe a multispecies epizootic ep·i·zo·ot·ic
Affecting a large number of animals at the same time within a particular region or geographic area. Used of a disease.
ep with genotypically identical M. tuberculosis strains. Their DNA fingerprint investigation showed that five of six animals had the identical strain and that zoo employees with previous negative tuberculin skin tests were exposed. Skin tests for 55 (18%) of 307 employees were positive, showing evidence of recent infection.
Bennett et al. (51) present data from the genotyping surveillance network with important policy implications. In addition to indicating that contact investigation should be extended to all settings frequented by the source case-patient, they also showed a significant positive association between being a smear-negative source case-patient and having unconfirmed transmission. This finding suggests that the identification of a smear-negative source case-patient (as an index case-patient) should not preclude the ongoing investigation for other possible sources. They also suggest that transmission from smear-negative case-patients is not negligible.
Sun et al. (52) report data gathered on transmission of tuberculosis to children <5 years of age. Representing a sentinel sentinel /sen·ti·nel/ (sen´ti-n'l) one who gives a warning or indicates danger.
a recording mechanism, such as an animal, a farm or a veterinarian, posted explicitly to record a possible occurrence or series of health event, thorough investigation of the circumstances of childhood tuberculosis remains critical to effective public health practice. They found that routine public health investigations conducted by local health departments, within the National Tuberculosis Genotyping and Surveillance Network, identified suspected source patients for 57 (51%) of 111 culture-confirmed case-patients <5 years of age. For 8 (15%) of these 57 patients, DNA fingerprinting suggested infection with different strains. These children were more likely to be older than other children and source case-patients with identical strains. The findings in this study highlight the requirement of rigorous case and contact investigation efforts, especially in household settings.
DNA Fingerprinting Laboratory Techniques Laboratory techniques are the sum of procedures used on natural sciences such as chemistry, biology, physics in order to conduct an experiment, all of them follow scientific method; while some of them involves the use of complex laboratory equipment from laboratory glassware to
Other articles in this issue present data that improve our understanding of both laboratory facets of DNA fingerprinting (i.e., IS6110 fingerprinting) and basic science of M. tuberculosis. Braden et al. (53) report the results of an external quality assessment program for the seven network laboratories in which the interlaboratory reproducibility was measured. They found that, overall, an exact match was achieved for 73% of isolates in panels: 90% matched with a one-band difference and 97% matched with a two-band difference. Although they report that final outcomes of pattern analysis and cluster determination in the genotyping surveillance network were probably closer to reality than the results of this quality assurance exercise suggest, they also warn that the variability and nonreproducibility, are substantial and should be considered when interpreting the results from the genotyping surveillance network. Crawford et al. (54) demonstrate through the establishment of the genotyping surveillance laboratory, that DNA fingerprinting remains an "art," and the experience and training of laboratorians are important.
Driscoll et al. (55) describe an evaluation of "logo analyses." Array-based assays use reverse hybridization hybridization /hy·brid·iza·tion/ (hi?brid-i-za´shun)
1. crossbreeding; the act or process of producing hybrids.
2. molecular hybridization
3. . The binary nature of array-based assays allows data to be analyzed usefully with algorithms associated with motif recognition, such as sequence logo analyses. Logo analyses have the potential to aid in visualizing and displaying spoligotyping cluster data and in managing the enormous amount of digital data generated by large-scale DNA fingerprinting projects. This potential is especially relevant now because low-incidence states and countries (including the United States) are considering universal implementation of DNA fingerprinting of M. tuberculosis. Using these and other bioinformatic tools, scientists will be able to interpret and understand the data generated by such a project.
Lok et al. (56) demonstrate that secondary typing methods (e.g., spoligotyping) should be used when isolates have no IS6100 insertions (i.e., zero-band strains). This article describes the differentiation power of secondary typing in these instances. In a second paper, Lok et al. (57) demonstrate the use and power of polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is techniques (e.g., variable number of tandem repeats This is a term from genetics, which describes a pattern that helps determine an individual's inherited traits.
Tandem repeats and variable number tandem repeats in DNA occur when a pattern of two or more nucleotides is repeated and the repetitions are directly adjacent to ) to distinguish and characterize the most common M. tuberculosis strain pattern in the United States--a two-band IS6110 RFLP pattern representing 5% of all isolates in the National Tuberculosis Genotyping Surveillance Network.
Diversity of M. tuberculosis Strains
The second important implication for DNA fingerprinting of M. tuberculosis is its ability to measure the overall diversity of M. tuberculosis strain patterns, including differences within the United States, differences by region and population, and prevalence of endemic strains. The genotyping surveillance network database demonstrated this diversity in the United States (57). The 10,883 patients in the study represent approximately 11.6% of all new TB cases in the United States from 1996 through 2000. Through this study, DNA fingerprinting of 10,883 isolates was performed by using the IS6110 RFLP method, yielding 6,128 distinct patterns.
Cowan et al. (58) report that family analysis of IS6110 patterns revealed 497 patterns related to the W-Beijing family (19); these patterns represent 946 isolates or 9% of all isolates in the genotyping surveillance network. Six new families of related DNA fingerprint patterns were also proposed for isolates containing 6-15 copies of IS6110. These families contain up to 251 patterns and 414 isolates; together, they contain 21% of isolates in this copy-number range and may represent endemic strains distributed across the United States.
The 8,245 isolates with more than six copies of IS6110 yielded 5,640 fingerprint patterns. Of these, 4,846 (86%) were identified for a single isolate, and 794 patterns grouped 3,399 isolates into fingerprint-defined clusters. Of 457 fingerprint patterns identified among the 2,507 isolates with low-copy numbers (six or fewer copies of IS6110), 314 (69%) were reported for a single isolate, and 143 grouped 2,193 isolates into clusters. Clustering was much greater among isolates with low-copy numbers (87%) than among isolates with high-copy numbers (41%).
Limitations, Challenges, and Future Considerations
The "state of the art" in applied DNA fingerprinting technology has scientific and molecular limitations, as well as stumbling blocks stum·bling block
An obstacle or impediment.
any obstacle that prevents something from taking place or progressing
Noun 1. to practical use in the field. The lack of reproducibility of the RFLP DNA fingerprinting technique and the difficulty in comparing patterns in an RFLP DNA fingerprint database remain important limitations in developing strategies for universal implementation. The other important factor related to RFLP is the time required for obtaining results. In order for DNA fingerprinting to provide value to routine contact investigations, these molecular data must be available on a timely basis, so that public health intervention health intervention Health care An activity undertaken to prevent, improve, or stabilize a medical condition specialists can use them in cluster investigations.
Furthermore, the precision of the interpretation of these data is evolving. Clustering, by itself and in its entirety, is not always equivalent to recent transmission; however, a portion of it is. The limitation of clustering interpretation must be scientifically established, especially if that interpretation is used as a marker for public health practice performance and as an indication of progress toward elimination of TB. We know that the population under study and the length of observation time play important roles in interpreting this measure. In addition, the specificity of the clustering case-definition factors into this equation. Additional investigation into this area is necessary.
How well these research techniques can be expanded to assist TB control programs is not clean Laboratory programs must be established to provide understandable, real-time results in a manner that influences decisions. The expansion of these techniques to assist TB control programs holds great promise. However, cluster investigation must be incorporated into routine public health practice, including the standardization standardization
In industry, the development and application of standards that make it possible to manufacture a large volume of interchangeable parts. Standardization may focus on engineering standards, such as properties of materials, fits and tolerances, and drafting of protocols. TB control officials require further training to interpret DNA fingerprinting results and act on these results in an effective way. The National Tuberculosis Controllers Association, in collaboration with the CDC, is currently drafting a DNA fingerprinting handbook to help health workers in the field understand and interpret DNA fingerprinting data.
We intend to continue analyses of the National Tuberculosis Genotyping and Surveillance Network data to gain additional insight into the value of cluster investigations. If DNA fingerprinting is to be implemented universally, this approach should be flexible enough to adapt to future laboratory techniques, as they become available. We think that DNA fingerprinting will become an essential tool in investigating TB transmission in difficult populations and unusual circumstances; consequently, DNA fingerprinting will be vital in the effort to eliminate TB.
The authors acknowledge the data management skill of Steve Kammerer and the valuable wisdom and counsel provided by Michael Iademarco, John Jereb, and Ken Castro.
This work was supported by the Centers for Disease Control and Prevention and the National Tuberculosis Genotyping and Surveillance Network.
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(2.) Jereb JA, Berwin DR, Dooley SW, Haas, WH. Nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital.
1. Of or relating to a hospital.
2. outbreak of tuberculosis in a renal transplant renal transplant Transplantation of a kidney from a living donor or cadaver to a recipient with ESRD Indications–children Congenital kidney/GU tract malformations–42%; focal segmental glomerulosclerosis-12% and others; 31% of children were ≤ age 5 unit: application of a new technique for restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates. J Infect Dis 1993;168:1219-24.
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Human immunodeficiency virus (HIV)
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(6.) Centers for Disease Control and Prevention. Targeted tuberculin testing tuberculin test
Any of various skin tests used to determine infection with Mycobacterium tuberculosis, in which tuberculin or its purified protein is introduced into the skin by injection or tines. and treatment of latent tuberculosis latent tuberculosis Infectious disease Infection with M tuberculosis that has been contained by the host's immune system and thus does not infect others Diagnosis Tuberculin skin test; release of IFN-γ in blood after PPD stimulation. See Tuberculosis. infection. MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg, Recomm Rep 2000;49:1-51.
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(9.) Bhattacharya M, Dietrich S, Mosher A mosher is a person who is crossed between goth/punk/skater they have long hair and listen to music like slipknot and metal music. Some people call them headbangers. At certain music shows they have something called a mosh pit, basically its a fight pit with loads of people bashing each other. L, Siddiqui F, Reisberg BE, Paul WS, et al. Cross-contamination of specimens with Mycobacterium tuberculosis: clinical significance, causes, and prevention. Am J Clin Pathol 1998;109:324-30.
(10.) Segal-Maurer S, Kreiswirth BN, Bums JM, Lavie S The Lavie was a French automobile manufactured in Paris around 1904. The company produced a few 6cv twin-cylinder voiturettes; one is reported to surive. Reference
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(12.) Van Duin JM, Pijnenburg JEM, van Rijswoud CM, de Haas de Haas as a surname can refer to:
WDH Windhoek, Namibia - Jg Strijdom (Airport Code)
WDH Washington Department of Health
WDH Width Depth Height
WDH Wireless Document Hosting , van Soolingen D. Investigation of cross contamination cross contamination Medical practice The passsage of pathogens indirectly from one Pt to another due to use of improper sterilization procedures, unclean instruments, or recycling of products in a Mycobacterium tuberculosis laboratory using IS6110 DNA fingerprinting. Int J Tuberc Lung Dis 1998;2:425-9.
(13.) Frieden TR, Woodley CL, Crawford JT, Lew D, Dooley SM. The molecular epidemiology molecular epidemiology Molecular medicine An evolving field that combines the tools of standard epidemiology–case studies, questionnaires and monitoring of exposure to external factors with the tools of molecular biology–eg, restriction endonucleases, of tuberculosis in New York City: the importance of nosocomial transmission and laboratory error. Tuber tuber, enlarged tip of a rhizome (underground stem) that stores food. Although much modified in structure, the tuber contains all the usual stem parts—bark, wood, pith, nodes, and internodes. Lung Dis 1996;77:407-13.
(14.) Braden CR, Templeton GL, Stead stead
1. The place, position, or function properly or customarily occupied by another.
2. Advantage; service; purpose: "His personal relationship with the electorate stands in good stead" WW, Bates Bates , Katherine Lee 1859-1929.
American educator and writer best known for her poem "America the Beautiful," written in 1893 and revised in 1904 and 1911. JH, Cave D, Valway SE. Retrospective detection of laboratory cross-contamination of Mycobacterium tuberculosis cultures with use of DNA fingerprint analysis. Clin Infect Dis 1997;24:35-40.
(15.) Northrup JM, Miller AC, Nardell E, Sharnprapai S, Etkind S, Driscoll J, et al. Estimated costs of false laboratory diagnoses of tuberculosis in three patients. Emerg Infect Dis 2002;8;1264-70.
(16.) Jasmer RM, Roemer M, Hamilton J, Bunter bunt 1
v. bunt·ed, bunt·ing, bunts
a. To bat (a pitched ball) by tapping it lightly so that the ball rolls slowly in front of the infielders.
b. J, Braden CR, Shinnick TM, et al. A prospective, multicenter study of laboratory cross-contamination of Mycobacterium tuberculosis cultures. Emerg Infect Dis 2002;8;1260-3.
(17.) Bradford WZ, Koehler J, El-Hajj H, Hopewell PC, Reingold AL, Agasino CB, et al. Dissemination of Mycobacterium tuberculosis across the San Francisco Bay area “Bay Area” redirects here. For other uses, see Bay Area (disambiguation).
The San Francisco Bay Area, colloquially known as the Bay Area or The Bay . J Infect Dis 1998;177:1104-7.
(18.) Ellis BA, Crawford JT, Braden CR, McNabb SJN SJN Scottsdale Job Network (Scottsdale, AZ)
SJN St. John Neumann , Moore M, Kammerer S, et al. Molecular epidemiology of tuberculosis in a sentinel surveilance population. Emerg Infect Dis 2002;8;1197-1209.
(19.) Bifani PJ, Plikaytis BB, Kapur V, Stockbauer K, Pan X, Lutfey ML, et al. Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family. JAMA JAMA
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(20.) Casper C, Singh SP, Rane S, Daley CL, Schechter GS, Riley LW, et al. The transcontinental transmission of tuberculosis: a molecular epidemiological assessment. Am J Public Health 1996;86:551-3.
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(22.) Valway SE, Sanchez MP, Shinnick TF, Orme I, Agerton T, Hoy Hoy, island, 13 mi (21 km) long and 6 mi (9.7 km) wide, off N Scotland, second largest of the Orkney Islands. It is located at the southwestern side of the Scapa Flow anchorage. D, et al. An outbreak involving extensive transmission of a virulent vir·u·lent
1. Extremely infectious, malignant, or poisonous. Used of a disease or toxin.
2. Capable of causing disease by breaking down protective mechanisms of the host. Used of a pathogen.
3. strain of Mycobacterium tuberculosis. N Engl J Med 1998;338:633-9.
(23.) Barclay DM III, Richardson JP, Fredman L. Tuberculosis in the homeless. Arch Fam Med 1995;4:541-6.
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(25.) Concato J, Rom WN. Endemic tuberculosis among homeless men in New York City. Arch Intern intern /in·tern/ (in´tern) a medical graduate serving in a hospital preparatory to being licensed to practice medicine.
in·tern or in·terne
n. Med 1994;154:2069-73.
(26.) Getberg L, Panarites C J, Morgenstern H, Leake B, Anderson RM, Koegel P. Tuberculosis skin testing among homeless adults. J Gen Intern Med 1997;12:25-33.
(27.) Layton MC, Cantwell MF, Dorsinville G J, Valway SE, Onorato IM, Frieden TR. Tuberculosis screening among homeless persons with AIDS living in single-room-occupancy hotels. Am J Public Health 1995;85:1556-9.
(28.) Pilote L, Tulsky JP, Zoiopa AR, Hanh JA, Schecter GF, Moss AR. Tuberculosis prophylaxis prophylaxis (prō'fĭlăk`sĭs), measures designed to prevent the occurrence of disease or its dissemination. Some examples of prophylaxis are immunization against serious diseases such as smallpox or diphtheria; quarantine to confine in the homeless. A trial to improve adherence to referral. Arch Intern Med 1996;156:161-5.
(29.) Zolopa AR, Hahn JA, Gorter R, et al. HIV and tuberculosis infection in San Francisco's homeless adults. JAMA 1994;272:455-61.
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(31.) McElroy PD, Sterling TR, Driver CR, Kreiswirth B, Woodley CL, Cronin WA, et al. Use of DNA fingerprinting to investigate a multiyear, multistate tuberculosis outbreak. Emerg Infect Dis 2002;8;1252-6.
(32.) Centers for Disease Control and Prevention. Outbreak of multidrug-resistant tuberculosis--Texas, California, and Pennsylvania. MMWR Morb Mortal Wkly Rep 1990;39:369-72.
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(35.) Glynn JR, Vynnycky E, Fine PEM (Privacy Enhanced Mail) A standard for secure e-mail on the Internet. It supports encryption, digital signatures and digital certificates as well as both private and public key methods. Not widely used, work on PEM later evolved into S/MIME. See MIME. . Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques. Am J Epidemiol 1999;149:366-71.
(36.) Vynnycky E, Nagelkerke N, Borgdorff MW, van Soolingen D, van Embden JDA JDA Japan Defense Agency
JDA Joint Development Agreement
JDA Janne da Arc (band)
JDA Joint Duty Assignment
JDA Jerusalem Development Authority
JDA Jovian Detention Authority (gaming) , Fine PEM. The effect of age and study duration on the relationship between `clustering' of DNA fingerprint patterns and the proportion of tuberculosis disease attributable to recent transmission. Epidemiol Infect 2001;126:43-62.
(37.) Murray M, Alland D. Methodological problems in the molecular epidemiology of tuberculosis. Am J Epidemiol 2002;155:565-71.
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(41.) Burman WJ, Reves RR, Hawkes AP, Reitmeijer CA, Yang Z, El-Hajj H, et al. DNA fingerprinting with two probes decreases clustering of Mycobacterium tuberculosis. Am J Respir Crit Care Med 1997;155:1140-6.
(42.) Braden CR, Templeton GL, Cave MD, Valway S, Onorato IM, Castro K, et al. Interpretation of DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. restriction fragment Noun 1. restriction fragment - the fragment of DNA that is produced by cleaving DNA with a restriction enzyme
fragment - a piece broken off or cut off of something else; "a fragment of rock" polymorphism polymorphism, of minerals, property of crystallizing in two or more distinct forms. Calcium carbonate is dimorphous (two forms), crystallizing as calcite or aragonite. Titanium dioxide is trimorphous; its three forms are brookite, anatase (or octahedrite), and rutile. analysis of M. tuberculosis isolates from a state with a large rural population. J Infect Dis 1997;175:1446-52.
(43.) Cronin WA, Golub JE, Lathan M J, Mukasa LN, Hooper N, Razeq JH, et al. Molecular epidemiology of tuberculosis in a low- to moderate-incidence state: are contact investigations enough? Emerg Infect Dis 2002;8;1271-9.
(44.) Miller AC, Sharnprapai S, Suruki R, Corkren E, Nardell EA, Driscoll JR, et al. Impact of genotyping of Mycobacterium tuberculosis on public health practice in Massachusetts. Emerg Infect Dis 2002;8;1285-9.
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(47.) Tabet SR, Goldbaum GM, Hooton TM, Eisenach KD, Cave MD, Nolan CM. Restriction fragment length polymorphism analysis detecting a community-based tuberculosis outbreak among persons infected with human immunodeficiency virus. J Infect Dis 1994;169:189-92.
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(49.) Chaves F, Yang Z, El Hajj hajj (häj), the pilgrimage to Mecca, Saudi Arabia, one of the five basic requirements (arkan or "pillars") of Islam. Its annual observance corresponds to the major holy day id al-adha, H, Alonso M, Burman W, Eisenach KD, et al. Usefulness of the secondary probe pTBN12 in DNA fingerprinting of Mycobacterium tuberculosis. J Clin Microbiol 1996;34:1118-23.
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(58.) Cowan LS, Crawford JT. Genotype genotype (jēn`ətīp'): see genetics.
Genetic makeup of an organism. The genotype determines the hereditary potentials and limitations of an individual. analysis of Mycobacterium tuberculosis isolates from a sentinel surveillance population. Emerg Infect Dis 2002;8; 1294-1302.
Scott J. N. McNabb, * Christopher R. Braden, * and Thomas R. Navin *
* Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Dr. McNabb is chief of the Epidemiologic Studies epidemiologic study A study that compares 2 groups of people who are alike except for one factor, such as exposure to a chemical or the presence of a health effect; the investigators try to determine if any factor is associated with the health effect Section, Surveillance and Epidemiology Branch, Division of Tuberculosis Elimination, Centers for Disease Control and Prevention; Project Officer for the National Tuberculosis Genotyping and Surveillance Network; and adjunct associate professor at the Rollins School of Public Health The Rollins School of Public Health (RSPH) is the public health school of Emory University. Founded in 1990, RSPH has more than 850 students pursuing master's degrees (MPH/MSPH) and over 100 students pursuing doctorate degrees (PhD). , Emory University Emory University (ĕm`ərē), near Atlanta, Ga.; coeducational; United Methodist; chartered as Emory College 1836, opened 1837 at Oxford. It became Emory Univ. in 1915 and in 1919 moved to Atlanta. . His primary research interests are public health surveillance, molecular epidemiology, and the primary prevention of allergic diseases.
Address for correspondence: Scott J. N. McNabb, Division of Tuberculosis Elimination National Center for HIV, STD, and TB Prevention The National Center for HIV, STD, and TB Prevention (NCHSTP) is a part of the Centers for Disease Control and Prevention and is responsible for public health surveillance, prevention research, and programs to prevent and control human immunodeficiency virus (HIV) infection and , Centers for Disease Control and Prevention, 1600 Clifton Road Clifton Road is main street in Clifton neighborhood of Saddar Town in Karachi, Sindh, Pakistan.
Its name dates from the British Colonial rule, and its market is posh areas of Karachi. , Mailstop E10, Atlanta, GA 30333, USA; fax: 404-639-8959; e-mail: email@example.com