Mycobacterium tuberculosis transmission between cluster members with similar fingerprint patterns. (Tuberculosis Genotyping Network).Molecular epidemiologic studies provide evidence of transmission of Mycobacterium tuberculosis Mycobacterium tuberculosis
Mycobacterium tuberculosis within clusters of patients whose isolates share identical IS6110-DNA fingerprint patterns. However, 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. transmission among patients whose isolates have similar but not identical DNA fingerprint DNA fingerprint
An individual's unique sequence of DNA base pairs. Also called genetic fingerprint. patterns (i.e., differing by a single band) has not been well documented. We used 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 , combined with conventional epidemiology, to show unsuspected patterns of tuberculosis transmission associated with three public bars in the same city. Among clustered TB cases, DNA fingerprinting analysis of isolates with similar and identical fingerprints helped us discover epidemiologic links missed during routine tuberculosis contact investigations.
The use of DNA fingerprinting has led to important advances in understanding the epidemiology of tuberculosis (TB) (1-5). However, Mycobacterium tuberculosis isolates that possess fewer than six copies of IS6110 do not generate sufficient polymorphism to be readily distinguishable by this technique and therefore require secondary genotyping with another probe (6). A few strains of M. tuberculosis lack IS6110 and cannot be fingerprinted with this technique (7,8). Although the epidemiologic importance of M. tuberculosis strains that have more than five copies of IS6110 with similar but not identical fingerprint patterns (differing by one or two IS6110 hybridizing bands) is unknown, in some cases epidemiologic links among patients infected with such strains have been established (9). Failure to identify these similar, but not identical, strains results in a misinterpretation of the extent of TB transmission in a community.
We conducted this study to determine the epidemiologic evidence of transmission among patients whose isolates have similar DNA fingerprint patterns (i.e., differing by a single band). Another purpose was to evaluate how useful such evidence, when combined with conventional epidemiology, would be in determining epidemiologic links that may have been missed during routine TB contact investigations in a cluster of patients.
We obtained M. tuberculosis isolates from persons whose cultures were positive for TB from the Arkansas Department of Health and from hospital and reference laboratories where clinical samples from Arkansas patients were submitted. At least one isolate was obtained for each person who had TB. During the period of study (January 1992-December 2000), we identified 1,977 patients with TB; 1,495 were culture positive. IS6110-based 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 ) analysis on the 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. extracted from the isolates of 1,141 patients (77% of culture-positive patients) was performed as described previously (10). Identical DNA fingerprint patterns are present when two or more patients' isolates have indistinguishable IS6110-DNA fingerprints of six or more bands or when isolates with fewer than six copies of IS6110 have identical RFLP patterns and secondary typing with polymorphic GC-rich sequence (PGRS PGRS Postal Grievance Research System (software) ) shows them to be indistinguishable (10-13). Similar DNA fingerprints exist when two or more patients' isolates share an IS6110-DNA fingerprint that differs by a single band (i.e., has an additional band [+ 1], lacks a band [- 1 ], or differs in the size of a single hybridizing band) and has an identical pattern by PGRS (1013). We performed secondary typing with PGRS for identical IS6110-based DNA fingerprint patterns with fewer than six bands or for patterns with six or more bands that were similar but differed by a single band (10-13).
When DNA fingerprints for isolates analyzed from 1992 to 2000 were reviewed for clustering, we identified a cluster of 15 TB patients. For all patients in the cluster, we examined routine TB contact investigation records, medical histories, and laboratory records. By using standard interviews, we established epidemiologic links among case-patients prospectively and retrospectively.
Eleven patients in the cluster resided in a small city in a predominantly rural county (county 1) with a population of 80,268 (14). The other four patients with isolates showing this DNA fingerprint resided in three other Arkansas counties, including one geographically contiguous to county 1. The other two counties were in different parts of the state and were not geographically contiguous to each other. Patients with isolates displaying this DNA fingerprint were not encountered at any other site during the study period.
The 15-patient cluster included 7 patients whose isolates had an identical 13-band fingerprint pattern (pattern A) and 5 patients whose isolates had a DNA-fingerprint pattern that differed by one less hybridizing band (pattern B). The DNA fingerprint pattern of isolates from three other patients differed from one of the two primary patterns by a single band. Secondary typing showed that all 15 case-patients had an identical PGRS pattern (Figure 1). Before DNA fingerprinting, routine contact investigations had established epidemiologic links for only four patients. After this cluster was discovered, epidemiologic investigations demonstrated that 12 of the patients resided in the two geographically contiguous counties, and 10 additional epidemiologic links were established among patients in the 15-member cluster (Figure 2).
[FIGURES 1-2 OMITTED]
Of seven patients (patients 1-7) with pattern A isolates, we discovered epidemiologic links for six. These six patients were connected to three local bars (i.e., commercial drinking establishments). TB was diagnosed for four of the six patients in 1992 and 1993. We found links between four patients connected to bar 1, including the bar's owner (patient 1), a bartender (patient 2), the bartender's husband (patient 3), and a patron (patient 4). Patient 4 also frequented bars 2 and 3. TB was diagnosed in 1996 for patient 5 and patient 6, who frequented bars 2 and 3, respectively. Patients 5 and 6 were in contact in these bars with patient 4 when he was infectious (Figure 2). Patient 7 was not linked to any of these bars; we found no epidemiologic links for him.
We found epidemiologic links for three of five patients who had pattern B isolates. TB was diagnosed in 1995 for the three patients; two (patients 8 and 9) frequented bar 2, and the third (patient 10) was a granddaughter of patient 9. We could not find epidemiologic links for two patients who had pattern B isolates. Patient 11 was a nurse at the local hospital; no TB patients had been admitted to the hospital where she worked, and she did not remember caring for any TB patients. Patient 12 did not reside in the same city or county. Both patients 11 and 12 denied frequenting any of the bars (Figure 2).
An indirect epidemiologic link was found for one (patient 13) of three patients (patients 13-15). Patient 13's isolate showed a DNA fingerprint pattern that differed from patterns A and B by a single band. Patient 13 was linked indirectly to patient 2 (bar 1) through acquaintances with patient 2's family members (patients 16-18); TB was diagnosed for these patients in 1991. DNA fingerprinting was not conducted for isolates from patients 16, 17, and 18 because they had TB before the beginning of the study (Figure 1). No epidemiologic links were discovered for patients 14 and 15.
Several factors are known to account for changes in RFLP patterns, including single nucleotide mutations that create a new restriction site restriction site
A site in a DNA segment in which the bordering bases are vulnerable to restriction enzymes. Also called cleavage site. or lead to loss of a preexisting pre·ex·ist or pre-ex·ist
v. pre·ex·ist·ed, pre·ex·ist·ing, pre·ex·ists
To exist before (something); precede: Dinosaurs preexisted humans.
v.intr. site. Insertions, duplications, inversions, and deletions can cause changes in restriction fragments. In IS6110 RFLP patterns, changes can also be accounted for by transposition transposition /trans·po·si·tion/ (trans?po-zish´un)
1. displacement of a viscus to the opposite side.
2. of the insertion sequence insertion sequence
Any of several discrete DNA sequences that repeat at various sites on a bacterial chromosome, on certain plasmids, and on bacteriophages and that can move from one site to another on the chromosome, to another plasmid in the same itself. Although the IS6110 RFLP pattern is sufficiently stable to enable us to make inferences about the linking of patients in a transmission chain, we have observed minor changes in the pattern (15).
DNA fingerprint clusters with similar but not identical IS6110-DNA fingerprint patterns should be investigated for epidemiologic links. In this investigation, we used secondary typing with PGRS and spoligotyping (data not reported) to show the isolates as indistinguishable. Previous studies demonstrate that the biological processes measured by PGRS typing or spoligotyping progress more slowly than those of transposable transposable /trans·pos·a·ble/ (trans-poz´ah-b'l) capable of being interchanged or put in a different place or order. elements like IS6110 (11). The molecular epidemiologic data indicate that the cases reported were caused by a strain of M. tuberculosis with the IS6110 RFLP pattern that diverged only recently.
During the period 1996-2000, 719 TB cases were confirmed by culture in Arkansas; 707 were genotyped by using IS6110. Of cases with isolates having more than five copies of IS6110, 234 were in 59 clusters ranging from 2-16 cases. Nineteen of these clusters, including 101 cases, included at least one isolate that was similar but not identical to other isolates in the cluster. In a preliminary study, we discovered epidemiologic links among 15% of patients with IS6110 RFLP patterns similar to those in clusters. During the same study period, we found epidemiologic links among 32% of Arkansas patients whose isolates shared an identical IS6110 RFLP pattern.
In this cluster investigation, we discovered additional epidemiologic links among 10 (66%) of 15 patients that were missed during routine contact investigations. In addition, the investigation helped us link eight (53%) of the patients in the cluster to three local bars as common sites of TB transmission (16,17). Our investigation highlighted an extensive social network with multiple epidemiologic links (18).
We gratefully acknowledge the contributions of Don Cunningham, Bill Starrett, and Susan Rowland.
The work described in this report was supported by the Veterans Administration and 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. Interagency Agreement 98FED10318. The authors used resources and facilities at the Central Arkansas Veterans Health Services health services Managed care The benefits covered under a health contract Center in Little Rock, Arkansas Little Rock, Arkansas
required military intervention to desegregate schools (1957–1958). [Am. Hist.: Van Doren, 556–557]
See : Bigotry .
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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. . An analysis by DNA fingerprint and conventional epidemiologic methods. N Engl J Med 1994;330:1710-6.
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(5.) Small PM, Shafer RW, Hopewell PC, Singh SP, Murphy MJ, Desmond E, et al. Exogenous reinfection reinfection /re·in·fec·tion/ (-in-fek´shun) a second infection by the same agent or a second infection of an organ with a different agent.
n. with multidrug-resistant Mycobacterium tuberculosis in patients with advanced 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. infection. N Engl J Med 1993;328:1137-44.
(6.) van Soolingen D, Hermans PWM (Pulse Width Modulation) A modulation technique that generates variable-width pulses to represent the amplitude of an analog input signal. Like its fixed-width pulse density modulation (PDM) cousin, the output switching transistor is on more of the time for a , Haas PEW, Soll DR, 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) . Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J Clin Microbiol 1991;29:2578-86.
(7.) van Soolingen D, Hermans PWM, Haas PEW, Groenen PMA PMA (papillary-marginal-attached),
n a system of epidemiologic scoring of periodontal disease devised by Schour and Massler in which the symbols denote the areas involved in gingival inflammation.
PMA Progressive muscular atrophy , van Embden JDA. Comparison of various repetitive DNA elements as genetic markers for strain differentiation and epidemiology of Mycobacterium tuberculosis. J Clin Microbiol 1993;31:1987-95.
(8.) Yuen LKW LKW Lastkraftwagen , Ross BC, Jackson KM, Dwyer B. Characterization of Mycobacterium tuberculosis strains from Vietnamese patients by Southern blot hybridization Southern blot hybridization Southern blotting Molecular biology A method delineated by EM Southern for detecting and manipulating specific DNA sequences previously separated by gel electrophoresis. . J Clin Microbiol 1993;31:1615-8.
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Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans. . J Infect Dis 1994;169:189-92.
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(14.) Fort Smith Chamber of Commerce. 2002. Available from: URL URL
in full Uniform Resource Locator
Address of a resource on the Internet. The resource can be any type of file stored on a server, such as a Web page, a text file, a graphics file, or an application program. : http:// www.fortsmith.org.
(15.) Cave MD, Eisenach KD, Templeton G, Salfinger M, Mazurek G, 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. J, et al. Stability of DNA fingerprint pattern produced with IS6110 strains of Mycobacterium tuberculosis. J Clin Microbiol 1994;32:262-6.
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Kashef Ijaz, * Zhenhua Yang, ([dagger]) H. Stewart Matthews, ([double dagger]) Joseph H. Bates, ([double dagger]) ([section]) and M. Donald Cave ([section]) ([paragraph])
* Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) University of Michigan (body, education) University of Michigan - A large cosmopolitan university in the Midwest USA. Over 50000 students are enrolled at the University of Michigan's three campuses. The students come from 50 states and over 100 foreign countries. , Ann Arbor, Michigan
“Ann Arbor” redirects here. For other uses, see Ann Arbor (disambiguation).
Ann Arbor is a city in the U.S. state of Michigan and the county seat of Washtenaw County. , USA; ([double dagger]) Arkansas Department of Health, Little Rock, Arkansas, USA; ([section]) University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) is part of the University of Arkansas System, a state-run university in the U.S. state of Arkansas. The main campus is located in Little Rock. , Little Rock, Arkansas, USA; and ([paragraph]) Central Arkansas Veterans Healthcare Services, Little Rock, Arkansas, USA
Dr. Ijaz worked with the Arkansas Department of Health TB Program as a medical epidemiologist conducting molecular epidemiology and DNA fingerprinting of Mycobacterium tuberculosis. In January 2002, Dr. Ijaz joined the Surveillance and Epidemiology Branch, Division of Tuberculosis Elimination, Centers for Disease Control and Prevention.
Address for correspondence: M. Donald Cave, University of Arkansas for Medical Sciences, 4301 W. Markham, Slot: 510, Little Rock, AR 72205, USA; fax: 501-664-6748; e-mail: email@example.com