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Worldwide occurrence of Beijing/W strains of Mycobacterium tuberculosis: a systematic review. (Synopsis).


Strains of the Beijing/W genotype genotype (jēn`ətīp'): see genetics.
genotype

Genetic makeup of an organism. The genotype determines the hereditary potentials and limitations of an individual.
 family of Mycobacterium tuberculosis Mycobacterium tuberculosis
n.
Tubercic bacillus.


Mycobacterium tuberculosis
 have caused large outbreaks of tuberculosis, sometimes involving multidrug resistance multidrug resistance,
n the adaptation of tumor cells or infectious agents to resist chemotherapeutic agents.
. This genetically highly conserved family 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 predominates in some geographic areas. We have conducted a systematic review of the published reports on these strains to determine their worldwide distribution, spread, and association with drug resistance. Sixteen studies reported prevalence of Beijing strains defined by spoligotyping; another 10 used other definitions. Beijing strains were most prevalent in Asia but were found worldwide. Associations with drug resistance varied: in New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of
, Cuba, Estonia, and Vietnam, Beijing strains were strongly associated with drug resistance, but elsewhere the association was weak or absent. Although few reports have measured trends in prevalence, the ubiquity Ubiquity
See also Omnipresence.



Burma-Shave

their signs seen as “verses of the wayside throughout America.” [Am. Commerce and Folklore: Misc.
 of the Beijing strains and their frequent association with outbreaks and drug resistance underline underline

an animal's ventral profile; the shape of the belly when viewed from the side, e.g. pendulous, pot-belly, tucked up, gaunt.
 their importance.

**********

In the early 1990s, a multidrug-resistant Mycobacterium tuberculosis strain was identified in New York (1). This strain, designated "W," which was associated with large institutional outbreaks of tuberculosis (TB) and many deaths, was later identified in other parts of 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.  (2,3). In 1995, a large proportion of the M. tuberculosis strains in the Beijing area of China was reported to have mutually highly similar multi-banded IS6110 restriction fragment-length 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.  (RFLP RFLP
abbr.
restriction fragment length polymorphism



RFLP

restriction fragment length polymorphism.

RFLP 
) patterns; these "Beijing" strains were also present in many other populations (4).

The 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.
 multidrug-resistant "W" strain was, in the second half of the 1990s, recognized as a member of the "Beijing" genotype family of M. tuberculosis strains (5-7). The W strain is recognized by a specific IS6110 fingerprint fingerprint, an impression of the underside of the end of a finger or thumb, used for identification because the arrangement of ridges in any fingerprint is thought to be unique and permanent with each person (no two persons having the same prints have ever been  pattern, by multiplex See multiplexing.  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  (PCR PCR polymerase chain reaction.

PCR
abbr.
polymerase chain reaction


Polymerase chain reaction (PCR) 
) targeted at specific insertions, or both (2,3). W family strains have IS6110 patterns closely related to that of W, although the degree of similarity in different studies has not always been specified. Beijing strains, including the W variants, have an insertion of IS6110 in the genomic dnaA-dnaN locus (5,7). All W family strains have a characteristic spoligotype that is shared with the whole Beijing family of strains and seems to be specific for this family (4,8,9). Spoligotyping is based on DNA polymorphism DNA polymorphism
n.
A condition in which one of two different but normal nucleotide sequences can exist at a particular site in a DNA molecule.
 in the direct repeat region, and "Beijing" spoligotypes only contain spacers 35-43.

The combination of a widespread family of strains and, in some situations, the association with multidrug resistance has led to concern that these strains may be spreading and may have a predilection for acquiring drug resistance. Many recent studies have recorded "Beijing-like" or "W-like" strains. We have conducted a systematic review of published reports to assess how widespread the family of strains is, whether there is any evidence that it is spreading, and whether it is associated with drug resistance.

Methods

Relevant studies were identified through computerized searches of Medline (January 1, 1990-November 1, 2001) and PubMed (January 1, 2000-November 1, 2001), manually searching key journals, searching the Internet, and crosschecking references with collections of articles on Beijing strains compiled by researchers in the field. The computerized searches used both thesaurus and free-text terms to search for tuberculosis and any of the following: 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, , 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 , DNA DNA: see nucleic acid.
DNA
 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.
 [fingerprint.sup.*], typing, type, types, 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, spoligotyping, [spoligotyp.sup.*], strain, and strains. The International Journal of Tuberculosis and Lung Disease lung disease Pulmonary disease Pulmonology Any condition causing or indicating impaired lung function Types of LD Obstructive lung disease–↓ in air flow caused by a narrowing or blockage of airways–eg, asthma, emphysema, chronic bronchitis; , its predecessor Tuberculosis and Lung Disease, and the Journal of Clinical Microbiology The Journal of Clinical Microbiology is an academic journal published by the American Society for Microbiology. The title is commonly abbreviated JCM and the ISSN is 0095-1137 for the print version, and 1098-660X for the electronic version.  were searched manually back to January 1990. A request for relevant articles was sent to all 32 participants in the European Union European Union (EU), name given since the ratification (Nov., 1993) of the Treaty of European Union, or Maastricht Treaty, to the

European Community
 Concerted Action project on New Generation Genetic Markers genetic marker
n.
A gene phenotypically associated with a particular, easily identified trait and used to identify an individual or cell carrying that gene.
 and Techniques for the Epidemiology and Control of Tuberculosis. An Internet search, using Google, used the term "Beijing strain tuberculosis." The reference lists of all included articles were searched for additional relevant studies.

Articles were included if they contained information allowing estimation of the proportion of TB patients included with the Beijing or W strains. Articles were excluded if they were limited to a particular outbreak, if they included only drug-resistant strains, or if <30 TB patients were included. Identified articles were subdivided into those that used spoligotyping to identify Beijing family strains and those that used other methods. Where spoligotypes were shown, estimates based on the spoligotype were used rather than any estimate given in the papers, using the proportion with spacers 35-43. Studies identifying only W strains or other W-like strains with a single IS6110 fingerprint pattern will underestimate the prevalence of Beijing strains, since they identify only part of the family of strains. The method of patient selection was recorded when stated. In all studies, any evidence of changes over time or by age group or of any association between strain type and drug resistance was recorded.

Results

Five thousand nineteen articles were selected from the initial search of Medline and PubMed. The titles and abstracts of these articles were scanned for relevant information, and 4,909 articles were rejected, leaving 110 articles for full text review. No further articles were identified by manual searching, but one recently published article was identified in the article collections that had not yet been indexed in the databases (10). One additional article was identified from reference list checking that was published in a Vietnamese journal not indexed by Medline, EMBASE, or Web of Science, and we have been unable to locate it. Another article was found from an Internet search, in an electronic journal (11). Of the 112 articles reviewed in full, 26 fulfilled the inclusion criteria
For Wikipedia's inclusion criteria, see: What Wikipedia is not.


Inclusion criteria are a set of conditions that must be met in order to participate in a clinical trial.
 of this review, including 16 that gave results based on spoligotyping and several that reported results from more than one area (Tables 1,2; Figure). Studies that described patients who were apparently included in other reports have been excluded (31,32).

[FIGURE OMITTED]

The Beijing strain was most common in the Beijing area of China, accounting for 92% of strains (4,12). The strain was common in all the Asian studies Asian studies is a field in cultural studies that is concerned with the Asian peoples, their cultures and languages. Within the Asian sphere, Asian studies combines aspects of sociology, and cultural anthropology to study cultural phenomena in Asian traditional and industrial  (4,8,12-15,23-25) and also in Houston, Texas “Houston” redirects here. For other uses, see Houston (disambiguation).
Houston (pronounced /'hjuːstən/) is the largest city in the state of Texas and the
 (25%), and Estonia (29%) (18,20). Some examples of the Beijing family were seen in almost all the populations studied (Tables 1 and 2).

Two studies looked at trends over time (Table 1). In China, the proportion of TB due to Beijing family strains in stored specimens going back to the 1950s was similar to the proportion among more recent specimens (12). In Gran Canaria Gran Canaria is the third largest island of the Canary Islands, an archipelago located in the Atlantic Ocean 210 km from the northwest coast of Africa and belonging to Spain. It is located southeast of Tenerife and west of Fuerteventura. , a dramatic increase was seen from 1992 to 1996, traced to an outbreak originating from a noncompliant patient with laryngeal laryngeal /lar·yn·ge·al/ (lah-rin´je-al) pertaining to the larynx.

la·ryn·geal or la·ryn·gal
adj.
Of, relating to, affecting, or near the larynx.
 TB (19). In studies over a short period, variations with age can be studied as a proxy for time trends. In Vietnam, among new cases of TB, the proportion due to Beijing strains was 71% in those <25 years of age, decreasing to 41% in those [greater than or equal to] 55 years (p < 0.001, chi square chi square (kī),
n a nonparametric statistic used with discrete data in the form of frequency count (nominal data) or percentages or proportions that can be reduced to frequencies.
 test for trend) (14). In Bangkok, little difference was seen with age in two studies (15,24). In Hong Kong Hong Kong (hŏng kŏng), Mandarin Xianggang, special administrative region of China, formerly a British crown colony (2005 est. pop. 6,899,000), land area 422 sq mi (1,092 sq km), adjacent to Guangdong prov.  (13), Jakarta, Indonesia (8), and Estonia (18), there was no association between age and disease due to the Beijing strain. In New Jersey, among those with tuberculosis due to W-like strains, 70% of patients were <50 years old, compared with 63% of those with other strains (p=0.2) (9). In Gran Canaria, the median age of cases with the Beijing strain was similar to that of all cases (19). No other studies have presented results by age.

Several studies reported associations with drug resistance (Table 3). Some studies found high rates of drug resistance among Beijing strains, but others found no difference in drug resistance profiles between Beijing and the other local strains.

An association between the successful spread of Beijing strains and BCG BCG bacille Calmette-Guérin.

BCG
abbr.
1. bacillus Calmette-Guérin

2. ballistocardiogram


BCG,
n.pr See bacille Calmette-Guórin.
 vaccination vaccination, means of producing immunity against pathogens, such as viruses and bacteria, by the introduction of live, killed, or altered antigens that stimulate the body to produce antibodies against more dangerous forms.  has been suggested (4). In Jakarta, Indonesia (8), 26% of those with Beijing strains and 23% of other patients had a BCG scar. In Vietnam, although a higher proportion of those with Beijing strains than with other strains had a BCG scar, this association was no longer apparent after the data were adjusted for age (14).

Discussion

This review has confirmed the ubiquity of the Beijing family of strains. Only a few of the smaller studies (in Martinique and French Guiana French Guiana (gēăn`ə, –än`–), Fr. La Guyane française, officially Department of Guiana, French overseas department (2005 est. pop. ) found no examples, and the proportion of TB due to Beijing strains in several Asian studies was >50%. However, studies could only be included in the review if they mentioned the Beijing strain or strain W or presented data showing spoligotypes. Some of the excluded studies may have found Beijing strains but not reported them as such (33,34). Others may have looked for Beijing strains but not reported negative findings. The only articles identified that reported not finding Beijing strains were studies including more than one study site. It is not known how unusual it is for a genotype family of M. tuberculosis to be as widespread as this. Comparable data are not available for other strains, although they are beginning to be gathered, and some other strains have also been found in several distinct settings (35).

In many studies, the true proportion of TB attributable to the Beijing family of strains is hard to assess. Difficulties arise due to the variable strain definitions used and the way patients were selected for inclusion. Spoligotyping seems to be both sensitive and specific for the Beijing family and is also easily compared between studies (6). Although IS6110 fingerprinting fingerprinting

Act of taking an impression of a person's fingerprint. Because each person's fingerprints are unique, fingerprinting is used as a method of identification, especially in police investigations.
 can also be used to detect this genotype family, with results that correlate closely with the spoligotypes, most published studies have used narrow definitions, based on a single strain or a few closely related strains defined by IS6110 fingerprinting; such studies are thus likely to underestimate the prevalence of Beijing strains. Studies including drug resistance in the definition (2) and those that appear to have defined the strains after grouping by drug resistance (26) may also underestimate the prevalence.

Some of the studies (those in the Netherlands, New Jersey, Houston, Texas, Gran Canaria, and French Guiana and the Caribbean islands) included information on all TB patients in the population and thus provide reliable estimates of prevalence. Others were less representative, and many did not state how the patients were selected (Table 1 and 2). Studies that included patients from particular hospitals may be representative of an area, but referral hospitals may be biased if they accept a high proportion of drug-resistant or complex cases. Similarly, convenience samples may not be representative of the community of TB patients, particularly if the samples were kept because they were interesting in some way (e.g., drug resistant or from epidemiologically related cases). TB patients in prison (10) may not have the same strains as those in the community. Some studies included only new patients, and others included both new patients and recurrent cases. This distinction, which was often not clear in the reports, could influence the results if relapse rates differ between strains.

In many studies, some culture-positive specimens are not typed because they are nonviable nonviable /non·vi·a·ble/ (-vi´ah-b'l) not capable of living.

non·vi·a·ble
adj.
Not capable of living or developing independently. Used especially of an embryo or fetus.
. IS6110 RFLP typing relies on large quantities of DNA and hence on viable strains, and theoretically some genotypes may survive better than others in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment.

in vi·tro
adj.
In an artificial environment outside a living organism.
. Spoligotyping is PCR-based so does not require viable isolates, but it is sometimes used only as a secondary method in specimens that have already been typed by IS6110 RFLP.

Associations with drug resistance were variable (Table 3): of the 12 studies with data available, only 4 found statistically significant increases in the proportions of drug resistance among those with Beijing strains. Of the Asian studies, only one found a statistically significant increase in drug resistance in Beijing strains (14), and in Hong Kong the Beijing strains were less likely than the others to be isoniazid isoniazid (ī'sōnī`əzĭd), drug used to treat tuberculosis. Also known as isonicotinic acid hydrazide, isoniazid is the most effective antituberculosis drug currently available.  resistant (13). In contrast, Beijing strains were strongly associated with drug resistance in New York, Cuba, and Estonia (3,18,21). In New York, the spread of the W strain, which was mainly nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital.

nos·o·co·mi·al
adj.
1. Of or relating to a hospital.

2.
 and institutional, has been attributed in part to drug resistance. Once a strain has become multidrug resistant, treatment is more complicated so patients may remain infectious for a longer period. Whether the Beijing family has a particularly high probability of acquiring drug resistance is not known but is suggested by the fact that these associations with the same strain family have been found in widely distributed Adj. 1. widely distributed - growing or occurring in many parts of the world; "a cosmopolitan herb"; "cosmopolitan in distribution"
cosmopolitan

bionomics, environmental science, ecology - the branch of biology concerned with the relations between organisms
 areas.

The published studies provided little direct evidence that the Beijing strain has been increasing. Of the two studies that included time trends, one found no increase in a population with a very high prevalence for many decades (12), and in the other the increase may be attributable to the characteristics of the index patient in the outbreak (19,36). In Vietnam, the proportion of new TB patients with the Beijing strain decreased with age, suggesting an increase in Beijing strains in the communities studied (14). No association with age was found anywhere else (8,9,13,15,18,19,24), including the two other studies restricted to new patients (13,18).

On the other hand, the ubiquity of the Beijing strain and its frequent appearance in outbreaks, particularly of drug-resistant TB, suggest that it may have the potential to spread. In Estonia, although there was no association between Beijing strains and age, TB and particularly multidrug-resistant (MDR MDR,
n See multidrug resistance.

MDR,
n the abbreviation for minimum daily requirement, specifically the Minimum Daily Requirements for Specific Nutrients compiled by the United States Food and Drug Administration.
) TB have been increasing, and most MDR TB was found to be due to Beijing strains (18). The limited amount of information available from most areas of the world and the possible biases in many of the studies make definite conclusions about the extent of spread and associations with drug resistance impossible. Through the European Concerted Action on New Generation Genetic Markers and Techniques for the Epidemiology and Control of Tuberculosis, a standard definition of the Beijing genotype is being finalized See finalization. , by comparisons of large collections of strains typed with spoligotyping, IS6110 RFLP, and Region A RFLP, which visualizes insertion of IS6110 in the genomic dnaA-dnaN locus (ms. in preparation). Studies are planned to reanalyze available data worldwide by using standard definitions and approaches.

Further studies are also needed to include more areas in an unbiased way, to study historical specimens if possible, and to investigate the virulence Virulence

The ability of a microorganism to cause disease. Virulence and pathogenicity are often used interchangeably, but virulence may also be used to indicate the degree of pathogenicity.
 (8) and transmissibility trans·mis·si·ble  
adj.
That can be transmitted: transmissible signals.



trans·mis
 of this potentially important family of M. tuberculosis strains. The question to be answered is if and to what extent Beijing genotype strains have selective advantages over other M. tuberculosis genotypes in the ability to gain resistance and to interact with the host immune defense system. If Beijing genotype strains represent a higher level of evolutionary development of M. tuberculosis being selected for as a result of the introduction of tuberculostatics, which inhibit the growth of M. tuberculosis, then consequences for the treatment of tuberculosis will be serious.
Table 1. Prevalence of Beijing family strains in studies that have used
spoligotyping (a)

Reference         Setting          Yrs           Population

Asia
12             Beijing and      1956-1960   Stored lung biopsy
              Hebei province,               samples from pneumo-
                   China                         nectomies
                                1969-1970
                                1979-1980
                                1989-1990
                                1956-1990
4             Beijing, China    1992-1994    ? Selection method
13               Hong Kong      1998-1999      Random sample
14              Ho Chi Minh     1998-1999      ? All patients
                 City, and
              Hanoi, Vietnam
15               Bangkok,       1999-2000       One hospital
                 Thailand                    ? Selection method
8                Jakarta,       1998-1999   Consecutive patients
                 Indonesia                       one clinic

Africa
16                Senegal       1994-1995    ? Selection method
                                             (all Beijing were
                                                 relapses)

Middle East
17             Fars Province    1995-1996     All from Shiraz;
                and Tehran,                 ? random for others
                   Iran

Europe
11              Northwest       1997-1998    ? Selection method
              region, Russia
10              Azerbaijan      1995-1996          Prison
                                             ? Selection method
18                Estonia         1994         Two hospitals,
                                                pulmonary TB
4               Netherlands     1993-1994     Whole population
19             Gran Canaria,    1991-1992       Whole island
                   Spain          1993
                                  1994
                                  1995
                                  1996
                                  1999

USA
9               New Jersey      1996-1998     Whole population
20            Houston, Texas    1994-1999     Whole population

Caribbean
21             Cuba, outside    1994-1995     Whole population
                  Havana
22              Guadeloupe      1994-1996       Whole island
22              Martinique      1995-1996       Whole island

South
America
22             French Guiana    1995-1996      Whole country

                                                         Prevalence
                                            New TB or      Beijing
Reference         Setting          Yrs      new + old   strain N/N (%)

Asia
12             Beijing and      1956-1960    ? Both       9/10 (90)
              Hebei province,
                   China
                                1969-1970                  8/9 (89)
                                1979-1980                18/18 (100)
                                1989-1990                 10/12 (83)
                                1956-1990                 45/49 (92)
4             Beijing, China    1992-1994    ? Both       45/49 (92)
13               Hong Kong      1998-1999     ? New      337/500 (67)
14              Ho Chi Minh     1998-1999      New       301/563 (53)
                 City, and
              Hanoi, Vietnam
15               Bangkok,       1999-2000    ? Both      90/204 (44)
                 Thailand
8                Jakarta,       1998-1999    ? Both       31/92 (34)
                 Indonesia

Africa
16                Senegal       1994-1995     Both        8/69 (12)

Middle East
17             Fars Province    1995-1996     Both        10/97 (10)
                and Tehran,
                   Iran

Europe
11              Northwest       1997-1998     Both       22/100 (22)
              region, Russia
10              Azerbaijan      1995-1996     Both        46/65 (71)
18                Estonia         1994         New       61/209 (29)
4               Netherlands     1993-1994     Both       82/2,594 (3)
19             Gran Canaria,    1991-1992    ? Both        0/85 (0)
                   Spain          1993                   10/179 (5.5)
                                  1994                   12/148 (8.1)
                                  1995                   18/110 (16)
                                  1996                   35/129 (27)
                                  1999                    9/40 (23)

USA
9               New Jersey      1996-1998     Both       68/1,207 (6)
20            Houston, Texas    1994-1999    ? Both     326/1,283 (25)

Caribbean
21             Cuba, outside    1994-1995    ? Both      20/157 (13)
                  Havana
22              Guadeloupe      1994-1996    ? Both        1/95 (1)
22              Martinique      1995-1996    ? Both        0/31 (0)

South
America
22             French Guiana    1995-1996    ? Both        0/76 (0)

(a) N/N, number with Beijing strain/total number of patients;

?, not clear from report.
Table 2. Prevalence of Beijing and W-like strains in studies not based
on spoligotyping (a)

Reference         Setting             Yrs             Population

Asia
23            Henan Province,          ?         No information given
                   China
23              Philippines            ?         No information given
23             Hanoi, Vietnam          ?         No information given
23                 Korea             1995        No information given
23                Thailand             ?         No information given
24                Bangkok          1994-1995       Patients from 3
            Nonthaburi, Thailand                   hospitals ? how
                                               selected. Half extrapul-
                                                        monary
23                Malaysia             ?         No information given
25                Malaysia         1993-1994    Random 3% sample from
                                                   whole population

Africa
26            Cape Town, South     1993-1997       Whole population
                   Africa

USA
27             New York City       1992-1994       Patients from 5
                                                      hospitals
3              New York City       1990-1995      ? selection method
28          Central Los Angeles    1994-1996     Consecutive patients
29               California        1992-1995   All cases from specific
                                                      locations
29                 Texas           1993-1995   All cases from specific
                                                      locations
29                Colorado         1989-1994   All cases from specific
                                                      locations
2              United States       1992-1997      All notified cases
             (excluding NY) and
                Puerto Rico

South
America
30             Buenaventura,       1997-1998   34 treatment failure +
                  Colombia                       73 new ? selection
                                                        method

                                   New TB or    Typing methods and
Reference         Setting          new + old      definitions used

Asia
23            Henan Province,          ?        RFLP +3.6kb Pvu II
                   China                              fragment
23              Philippines            ?        RFLP +3.6kb Pvu II
                                                      fragment
23             Hanoi, Vietnam          ?        RFLP +3.6kb Pvu II
                                                      fragment
23                 Korea               ?        RFLP +3.6kb Pvu II
                                                      fragment
23                Thailand             ?        RFLP +3.6kb Pvu II
                                                      fragment
24                Bangkok           ? Both       RFLP + comparison
            Nonthaburi, Thailand                with Dutch database
23                Malaysia             ?        RFLP +3.6kb Pvu II
                                                      fragment
25                Malaysia          ? Both       RFLP "similar" to
                                                   Beijing family

Africa
26            Cape Town, South       Both        RFLP "strain U",
                   Africa                      (W-like) Two closely
                                               related patterns only

USA
27             New York City        ? Both      RFLP, strain W only
3              New York City        ? Both         RFLP, "W-like"
28          Central Los Angeles     ? Both       RFLP, strain 210
                                                    (W-related)
29               California         ? Both       RFLP, strain 210
                                                    (W-related)
29                 Texas            ? Both       RFLP, strain 210
                                                    (W-related)
29                Colorado          ? Both       RFLP, strain 210
                                                    (W-related)
2              United States         Both      RFLP and/or PCR probe.
             (excluding NY) and                Multidrug resistant W
                Puerto Rico                             only

South
America
30             Buenaventura,         Both        RFLP + PCR probe.
                  Colombia                         "Similar" to W

                                     Prevalence of
                                    Beijing strain
Reference         Setting               N/N (%)

Asia
23            Henan Province,         59/64 (92)
                   China
23              Philippines           34/34 (100)
23             Hanoi, Vietnam         20/50 (40)
23                 Korea              99/138 (72)
23                Thailand            31/49 (63)
24                Bangkok             80/211 (37)
            Nonthaburi, Thailand
23                Malaysia            17/48 (35)
25                Malaysia            83/439 (19)

Africa
26            Cape Town, South       17/650 (2.6)
                   Africa

USA
27             New York City          6/302 (2.0)
3              New York City        273/1,953 (14)
28          Central Los Angeles       43/162 (27)
29               California           39/522 (7)
29                 Texas              16/546 (3)
29                Colorado            2/256 (0.8)
2              United States       23/104,549 (0.02)
             (excluding NY) and
                Puerto Rico

South
America
30             Buenaventura,          11/107 (10)
                  Colombia           (? 8 in new)

(a) N/N, number with Beijing strain/total number of patient;

?, not clear from report; the different typing methods are described in
the introduction.

RFLP; restriction fragment length polymorphism using IS6110.

PCR; Polymerase chain reaction probe is a multiplex PCR probe targeted
at specific insertions. The 3.6 kb pvuII fragment was identified by
IS1081 fingerprinting.
Table 3. Association between Beijing family strains of Mycobacterium
tuberculosis and drug resistance (a)

                                              % Drug resistance

                                Strain               Any

                                     Non-                Non-
Reference    Place, yr    Beijing   Beijing   Beijing   Beijing

13          Hong Kong,      310       181
             1998-1999

14            Ho Chi        264       235
            Minh City,
             1998-1999

15           Bangkok,       90        114
             1999-2000

8            Jakarta,       27        56        41        25
             1998-1999

16           Senegal,        8        61
             1994-1995

11          NW Russia,      22        78
             1997-1998

10          Azerbaijan,     46        19        89        68
             1995-1996

18           Estonia,       61        148       70        14
               1994

19             Gran         75        576        0         ?
             Canaria,
             1991-1996

3            New York,      273      1,680
             1990-1995      (W-     (not W
                           like)     like)

21 (d)         Cuba,        20        137      55-65      4-5
             1994-1995

30           Colombia,      11        70
             1997-1998

                                    % Drug resistance

                                  I                   S

                                     Non-                Non-
Reference    Place, yr    Beijing   Beijing   Beijing   Beijing

13          Hong Kong,       6        12        10        13
             1998-1999

14            Ho Chi        28        19        42        19
            Minh City,
             1998-1999

15           Bangkok,
             1999-2000

8            Jakarta,       37        20        15         5
             1998-1999

16           Senegal,
             1994-1995

11          NW Russia,
             1997-1998

10          Azerbaijan,     80        68        83        58
             1995-1996

18           Estonia,
               1994

19             Gran
             Canaria,
             1991-1996

3            New York,
             1990-1995

21 (d)         Cuba,       55-60       4       0-10      0.7-2
             1994-1995

30           Colombia,
             1997-1998

                          % Drug resistance

                                 MDR
                                               Comparison of Beijing
                                     Non-     vs. non-Beijing by drug
Reference    Place, yr    Beijing   Beijing      (b) RR 95% CI (b)

13          Hong Kong,                         I 0.54 (0.30 to 0.97)
             1998-1999                          S 0.76 (0.46 to 1.3)

14            Ho Chi       3           2         I 1.5 (1.1 to 2.0)
            Minh City,                           S 2.2 (1.6 to 3.0)
             1998-1999                         MDR 1.4 (0.47 to 4.3)

15           Bangkok,                                 No assoc
             1999-2000

8            Jakarta,                          Any 1.6 (0.86 to 3.1)
             1998-1999                          I 1.9 (0.92 to 3.9)
                                                S 2.8 (0.67 to 11.5)

16           Senegal,                                 No assoc
             1994-1995

11          NW Russia,    77          58        MDR 1.3 (1.0 to 1.8)
             1997-1998

10          Azerbaijan,   61          32       Any 1.3 (0.94 to 1.8)
             1995-1996                          I 1.2 (0.84 to 1.6)
                                                S 1.4 (0.95 to 2.1)
                                               MDR 1.9 (0.96 to 3.9)

18           Estonia,     34           2        Any 5.0 (3.2 to 7.6)
               1994                            MDR 17.0 (5.3 to 54.9)

19             Gran
             Canaria,
             1991-1996

3            New York,    93 (c)      ?0              p <0.001
             1990-1995

21 (d)         Cuba,       0          0.7      Any 10.8 (4.7 to 24.5)
             1994-1995                          I 15.1 (5.8 to 38.9)

30           Colombia,    27          23       MDR 1.2 (0.41 to 3.4)
             1997-1998

(a) I, isoniazid; S, streptomycin; MDR, multidrug resistant (at least
isoniazid and rifampicin); blank spaces indicate that data are not
available.

(b) Relative risks (RR) were calculated when possible from the data
presented. These are shown with 95% confidence intervals.

(c) Resistant to at least four drugs. Includes 206 W strains and 40 W1
strains. Identified by RFLP, not spoligotyping.

(d) Exact numbers not clear since drug resistance data only given by
strain number for IS6110 defined clusters, and two Beijing strains were
not clustered. For the relative risk calculation, the minimum proportion
resistant among the Beijing strains was used.


Acknowledgments

We thank Martien Borgdorff for helpful comments on an earlier draft.

This paper was written as part of the EU Concerted Action project QLK2-CT-2000-00630. JRG JRG joint review group (US DoD)
JRG Junta Revolucionaria de Gobierno (Revolutionary Governing Junta; El Salvador)
JRG Jim Roberts Group
 is partially funded by the Department for International Development, United Kingdom.

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Dr. Glynn is a senior lecturer senior lecturer
n. Chiefly British
A university teacher, especially one ranking next below a reader.
 in epidemiology at the London School of Hygiene and Tropical Medicine tropical medicine, study, diagnosis, treatment, and prevention of certain diseases prevalent in the tropics. The warmth and humidity of the tropics and the often unsanitary conditions under which so many people in those areas live contribute to the development and , London, United Kingdom. Her research interests include tuberculosis, 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. , and molecular epidemiology.

Address for correspondence: Judith Glynn, Department of Infectious and Tropical Diseases Tropical diseases are infectious diseases that either occur uniquely in tropical and subtropical regions (which is rare) or, more commonly, are either more widespread in the tropics or more difficult to prevent or control. , London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK; fax: 44-(0)-20-7636-8739; e-mail: judith.glynn@lshtm.ac.uk

Judith R. Glynn, * Jennifer Whiteley, * Pablo J. Bifani, ([dagger]) Kristin Kremer, ([double dagger double dagger
n.
A reference mark () used in printing and writing. Also called diesis.

Noun 1.
]) and Dick van Soolingen ([double dagger])

* London School of Hygiene and Tropical Medicine, London, UK; ([dagger]) Institut Pasteur de Lille, France; and ([double dagger]) National Institute of Public Health and the Environment (RIVM RIVM Rijksinstituut voor Volksgezondheid en Milieu ), Bilthoven, the Netherlands
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Author:van Soolingen, Dick
Publication:Emerging Infectious Diseases
Article Type:Statistical Data Included
Geographic Code:4EUUK
Date:Aug 1, 2002
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