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Journal of Clinical Microbiology, June 2001, p. 2213-2218, Vol. 39, No. 6
Institute of Infectious Diseases and Tropical
Medicine, L. Sacco Hospital, University of
Milan,1 and Villa Marelli
Institute,2 Milan, and Clinic of
Infectious Diseases, Spedali Civili, University of Brescia,
Brescia,3 Italy
Received 27 December 2000/Returned for modification 29 January
2001/Accepted 8 April 2001
In geographical areas with a low incidence of tuberculosis,
recurrent tuberculosis is generally due to reactivation of the disease.
However, the relative contribution of tuberculosis reinfection increases in parallel with the incidence of disease and is likely to
depend on the epidemiological context: factors such as the spread of
multidrug resistance, human immunodeficiency virus (HIV) infection, and
immigration from developing countries could modify disease transmission
in areas at low risk for tuberculosis. A molecular epidemiology study
was performed in Lombardy, Northern Italy, where the incidence of
tuberculosis is 17.5 cases per 100,000 persons. A total of 2,452 cases
of culture-confirmed tuberculosis in 2,127 patients were studied. A
group of 32 patients (1.5%), each of whom had two episodes of
tuberculosis with cure as the outcome of the first episode and with
more than 6 months between the two episodes, were studied by means of
restriction fragment length polymorphism DNA fingerprinting analysis.
For 5 of the 32 patients (16%), the DNA fingerprinting patterns of
Mycobacterium tuberculosis strains responsible for the
second episode did not match those of the corresponding isolates of the
first episode, indicating exogenous reinfection. Two of these patients
developed multidrug-resistant tuberculosis during the second episode,
and in three cases the isolates belonged to clusters of M. tuberculosis strains spreading in the community. A
fourfold-increased risk for reinfection was observed in immigrant
patients compared to Italian subjects. In contrast, a higher risk of
relapse rather than reinfection was evidenced in HIV-positive subjects
and in patients infected with multidrug-resistant tuberculosis.
Episodes of tuberculosis reinfection in areas with a low incidence of
tuberculosis are rare compared to those in high-incidence geographical
regions. In populations that have immigrated from high-risk areas,
reinfection may represent a considerable contributor to the rate of
recurrent tuberculosis. This finding emphasizes the importance of
containing the spread of epidemic strains in close communities, in
order to prevent changes in global tuberculosis trends for developed countries.
Active tuberculosis in patients with
prior tuberculous infection can occur following endogenous reactivation
or exogenous reinfection. For decades, the issue of the role of
exogenous reinfection has been debated. Recent models based on
estimates of the annual risk of infection and the incidence of
tuberculosis have suggested that the relative contribution of exogenous
reinfection increases in parallel with the incidence of the disease
(2, 26). Molecular biology-based methods have been shown
useful in differentiating Mycobacterium tuberculosis
strains, demonstrating whether a new episode of tuberculosis is caused
by infection with the same strain as the previous episode or by a
different strain (7, 20). Recently, a study carried out in
a metropolitan area of South Africa, using DNA fingerprinting to
examine isolates of M. tuberculosis, found evidence that
exogenous reinfection can have a dominant role in the pathogenesis of
postprimary tuberculosis in an area with a high incidence of the
disease (24). A different scenario could be evoked for a
population with a low risk of infection, where the likelihood of
reexposure is small and thus most cases of recurrence probably result
from relapse. However, specific phenomena, such as the emergence of
human immunodeficiency virus (HIV)-related tuberculosis outbreaks or
immigration from high-incidence countries, could modify the evolution
of tuberculosis transmission. Since 1993, Northern Italy has been our
point of observation for investigating some aspects of this issue by
means of molecular epidemiology techniques. The occurrence of
tuberculosis in the Lombardy region was characterized by a general
increase in the early 1990s, with immigrants and HIV-infected patients
as the most important sources of tuberculosis among the younger age
groups. The resurgence of tuberculosis in this area has also been
accompanied by alarming outbreaks of the disease caused by organisms
resistant to multiple antituberculous drugs (9, 10, 14). A
large proportion of patients infected with these organisms have been coinfected with HIV, and the fatality rate has been extremely high.
More recently, the global incidence of tuberculosis has begun to
decrease again, but cases among immigrants are still on the increase in
both absolute and relative terms. During the period between 1993 and
1996, the approximate annual rates for Italian-born and immigrant
patients were 14.4 per 100,000 and 109 per 100,000, respectively
(4).
In this study we determined the relative frequencies of relapse and
exogenous reinfection, using DNA fingerprinting for patients with
episodes of recurrent tuberculosis in a geographic area where the risk
of infection is low but where tuberculosis outbreaks among HIV-infected
patients, caused by organisms resistant to multiple antituberculous
drugs, have been reported in recent years. We also considered the
possible role of immigrants from developing countries in maintaining a
high rate of tuberculosis reinfection in the population.
Patient population and data collection.
All tuberculosis
cases, confirmed by examination of cultures, from the Reference Centre
for Tuberculosis Control of Lombardy, Villa Marelli, and from two
representative infectious diseases in Lombardy wards (L. Sacco Hospital
of Milan and Spedali Civili of Brescia) were included in this study.
Lombardy is the most highly populated region of Northern Italy (about 9 million inhabitants) and accounts for as many as 30% of Italian AIDS
cases, with a considerable concentration of immigrants from developing
countries. In 1995 we initiated a prospective survey study in which all
collected cultures positive for M. tuberculosis were
genotyped by restriction fragment length polymorphism (RFLP)
fingerprinting and spoligotyping analysis (for M. tuberculosis isolates with fewer than five bands). A database of
the results was also established. Patients included in this study had
at least two episodes of tuberculosis, with cure as the outcome of the
first episode, within the study period (between January 1995 and
December 1999). Cure was defined as the completion of a course of 6 months of combination therapy, a sputum culture positive for M. tuberculosis at diagnosis, and at least one negative sputum
culture at the end of treatment. Recurrence was defined as development
of a culture positive for M. tuberculosis and symptoms
consistent with tuberculosis after the patient had completed a course
of treatment and had been confirmed culture negative and clinically
recovered. Patients who needed treatment for a subsequent episode but
who did not meet criteria for cure, since less than 6 months had
elapsed between the two episodes, were considered "not cured" and
were excluded from the study. A patient whose M. tuberculosis isolates from the first and second episodes were
different upon RFLP analysis was considered to have tuberculosis due to
a new, exogenous reinfection. Clinical records of the patients were
obtained, including data on age, sex, country of birth, date of arrival
in Italy (for the immigrants), medical status with regard to HIV
infection, drug susceptibility, treatment, and outcome.
Clinical specimen collection.
Primary mycobacterial
isolation was performed using Löwenstein-Jensen slant cultures
and a radiometric method (BACTEC; Middlebrook 7H12; Becton Dickinson,
Diagnostic Instrumental System, Towson, Md.). Drugs and concentrations
used for susceptibility testing for M. tuberculosis isolates
included isoniazid (1 mg/µl), ethambutol (5 mg/µl), rifampin (1 mg/µl), and streptomycin (10 mg/µl).
RFLP DNA fingerprinting analysis.
DNA extraction, digestion,
and Southern blotting were carried out as described previously
(25). M. tuberculosis isolates were genotyped
by RFLP fingerprinting analysis using the IS6110 probe as a
genetic marker, as previously described by van Embden et al.
(23).
Spoligotyping method.
Spoligotyping, a PCR method based on
the polymorphic direct-repeat (DR) region containing 36-bp direct
repeats and interspersed 35- to 41-bp variable spacer sequences, was
performed on genomic DNA by standard methods as previously described by
Kamerbeek and others (13, 22).
Computer-assisted analysis of the patterns.
GelCompar
software, version 4.1 (Applied Maths BVBA, Kortrijk, Belgium), was used
to compare the hybridization patterns obtained by RFLP DNA
fingerprinting and spoligotyping. After the results of the analysis,
each patient's isolate were compared with our database, which contains
more than 3,000 DNA patterns derived from tuberculosis cases analyzed
from January 1994 to March 2000, to determine whether the isolates
belonged to a cluster or were unique within the communities studied.
Statistical analysis.
Differences in rates of tuberculosis
reinfection or relapse between groups were assessed by Fisher's exact
test and the chi-square test with the Pearson correlation coefficient.
Univariate and multivariate analyses were performed, evaluating crude
and adjusted risks through a logistic regression model. Statistical
significance was defined as a P value of <0.05.
During the study period (January 1995 through December 1999) a
total of 2,452 M. tuberculosis cultures from 2,127 patients were available for RFLP analysis. Italian citizens accounted for 86%
of the episodes, and immigrants accounted for 14% of the episodes. Among the 2,127 patients, 448 (21%) were known to be infected with
HIV. Thirty-two of the 2,127 patients (1.5%) met the selection criteria, in that they had two successive episodes of pulmonary tuberculosis within the study period with more than 6 months between those two episodes. The median age was 49 years. The median interval between cure and subsequent diagnosis was 19 months (range, 7 to 60 months). Of the 32 patients with tuberculosis relapse, 6 were
immigrants from developing countries (1 from Senegal, 2 from Peru, 1 from China, 1 from Morocco, and 1 from Brazil) (Table 1).
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.6.2213-2218.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Molecular Epidemiology Study of Exogenous
Reinfection in an Area with a Low Incidence of
Tuberculosis
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
RESULTS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
TABLE 1.
Characteristics of 32 patients with tuberculosis
recurrence
In 5 cases (16%) the RFLP patterns of the M. tuberculosis
strains responsible for the episode of recurrence did not match those
of the corresponding isolates of the first episode, indicating exogenous reinfection, whereas 27 patients (84%) had the same DNA
fingerprinting for both episodes of tuberculosis (Fig.
1).
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Three of the five patients with presumed exogenous reinfection were Italian (one of whom was positive for HIV infection), and two were HIV-negative immigrants from developing countries (Senegal and Peru). Two patients whose initial isolates had been drug-sensitive strains had organisms resistant to isoniazid and rifampin during the second, genotypically different episode. Two patients had episodes caused by two different drug-sensitive strains. The last patient initially had a drug-resistant isolate that caused two successive episodes of pulmonary tuberculosis; 8 months after the beginning of the second episode, a drug-sensitive strain of M. tuberculosis showing a different RFLP type was isolated. Isolates from the five patients with presumed reinfection were studied in relation to the complete RFLP database. Of the M. tuberculosis isolates responsible for the first episode, only one belonged to a cluster of strains present in the community. The isolates responsible for reinfection in three of five cases belonged to clusters of M. tuberculosis strains present in the community; for the remaining two isolates no matching strains were identified in the database. One of the clustered strains isolated from an HIV-negative immigrant patient was a drug-sensitive strain belonging to a cluster containing only two other strains, both found in HIV-negative Italian patients. The other two clustered strains responsible for exogenous reinfection were multidrug resistant: the first, found in an Italian HIV-positive patient, matched another strain isolated from a 92-year-old Italian HIV-negative patient; the other was a multidrug-resistant strain of Mycobacterium bovis isolated from an Italian HIV-negative patient. Genotypic analysis performed by both IS6110 RFLP and spoligotyping showed that this strain originated from a large outbreak which occurred in an Infectious Diseases Department in Lombardy between March 1993 and May 1995, involving 37 HIV-positive patients and 3 HIV-negative patients.
The other 27 patients (84%) showed two identical RFLP patterns for the two episodes, suggesting endogenous reactivation. Nine patients (33%) were HIV positive. Four patients (15%) were immigrants from developing countries: two HIV-positive patients (from Brazil and Peru) and two HIV-negative patients (from Morocco and China). For 15 patients with the same isolates at the initial and the second episode (56%), the isolates responsible for both episodes showed multidrug resistance. The multidrug-resistant isolates responsible for reactivation in 12 of 15 cases belonged to clusters of strains present in the community. The molecular definition of exogenous reinfection used in this study excludes the possibility of exogenous reinfection with the identical strain. Therefore, it is possible that some of the patients considered to have relapses actually had new, exogenous reinfection with the same strain. Our results may thus underestimate the extent of exogenous reinfection. Among the 12 cases of infection with multidrug-resistant strains, 7 isolates associated with different nosocomial epidemics spreading in our region mainly involving HIV-positive patients. Among the drug-sensitive strains responsible for endogenous reactivation, 7 out of 12 belonged to clusters. Two were isolated from HIV-positive patients (a Brazilian and an Italian patient) sharing the same RFLP typing with other Italian patients with HIV infection (four patients for each cluster). The drug-sensitive strains isolated from five Italian patients without HIV infection were included in different clusters containing only isolates from Italian patients (both HIV positive and HIV negative) (two patients for each cluster).
The rates of reinfection were analyzed for different groups:
HIV-positive versus HIV-negative patients, Italian residents versus
immigrants, drug-susceptible versus drug-resistant isolates. Reinfection occurred in 3 (11.5%) of 26 Italian patients and in 2 (33.3%) of 6 immigrant patients. Reinfection was less frequent in
patients with multidrug-resistant strains responsible for the first
episode (11.8%) than in those who had a first episode sustained by
susceptible strains (20%). Reinfection was less common among HIV
patients (10%) than among patients without HIV infection (18.2%) (Table 2).
|
Results of multivariate analysis did not show any significant
association. However, the analysis evidenced a fourfold risk of
reinfection among immigrant patients (adjusted risk, 4.7; 95% confidence interval [95% CI], 0.48 to 45.9) compared to Italian patients. HIV infection was associated with a one-half risk of reinfection (adjusted risk, 0.45; 95% CI, 0.036 to 5.46), and the
isolation of multidrug-resistant strains in the first episode was
correlated with a one-third risk of reinfection (adjusted risk, 0.35;
95% CI, 0.0098 to 12.8) (Table 3).
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DISCUSSION |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
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The possibility of persons previously infected with M. tuberculosis being exogenously reinfected has been debated for
decades. However, it was supposed to occur rarely because of the
immunity conferred by initial infection. The extent to which exogenous reinfection occurs depends on the prevalence of disease
the higher the
prevalence, the greater the likelihood of exogenous reinfection (8, 19). On the few occasions on which exogenous
reinfection has been documented in areas with a low incidence of the
disease, it has involved only selected populations, for example,
alcoholic residents of a homeless shelter or patients with advanced HIV infection (3, 11, 16, 21).
Our study confirmed that reinfection in areas with a low incidence of tuberculosis is possible, although less common than in high-incidence geographical regions, indicating that higher prevalence of M. tuberculosis represents the major risk for tuberculosis reinfection (24). Relapse of a previous infection remains, in our region, the more probable cause of recurrence. However, this scenario could be susceptible to change in the future, due to social, microbiological, and epidemiological factors. Using multivariate analysis we found no significant association between HIV, immigration, multidrug resistance, and the rate of reinfection. However, we observed a fourfold higher risk of reinfection in immigrant patients compared to Italian subjects. Cohesiveness within ethnic communities, overcrowding, and poor hygienic conditions allow for an elevated frequency of close contacts, with a consequent high circulation of M. tuberculosis strains, that could explain the increased risk of reinfection. This phenomenon plays a major role for immigrants coming from areas with a high incidence of tuberculosis. In a previous study on immigrants from developing countries, we demonstrated that the M. tuberculosis clustering ratio varies among immigrant groups, reflecting mostly the duration of stay in Italy and the social behaviors of the immigrants (4).
Recurrence of tuberculosis is a frequent event among HIV populations (6, 15, 17). We showed that HIV-infected patients were more prone to recurrences than people without HIV infection. The HIV patients had twice the risk of reactivation of a previous M. tuberculosis episode, demonstrated by correspondence of the RFLP genotypes. It is well known that the rate of relapse of infection due to the same M. tuberculosis strain is high in HIV-positive populations, especially in association with a low CD4+ cell count and with a duration of treatment shorter than 9 months (1, 12, 18, 27). Even though recent studies have shown similar rates of tuberculosis relapse in HIV-positive and HIV-negative patients after successful directly observed therapy (5), the higher occurrence of relapse in our HIV-positive population could be first explained by the low compliance of our patients (frequently intravenous drug users) with the antituberculosis treatment. Due to inadequate drug adherence, an apparent clinical and microbiological response was observed after the first episode, regardless of incomplete elimination of M. tuberculosis bacilli. Moreover, in our region, the emergence of multidrug-resistant tuberculosis outbreaks among HIV-positive patients had been a critical issue. The difficulty of finding sustained successful treatments for those particular strains associated with the immunological decline of HIV-positive patients has represented a key factor for the increased risk of reactivation of multidrug-resistant disease.
The importance of multidrug-resistant strains was also evaluated in our study, which detected an increased risk of relapse in patients whose first episode was attributable to multidrug-resistant strains, compared to those whose first episode was caused by susceptible strains. This observation confirms the difficulty of treating and eradicating multidrug-resistant tuberculosis, mainly when associated with HIV infection and low compliance of patients.
In conclusion, our data seem to confirm that reinfection is possible among people in developed countries, but at rates lower than those in high-risk areas. However, this scenario could be modified in the future by the presence of high-risk populations. In particular, for immigrant populations from high-risk areas, especially when they live in poor socioeconomic conditions, reinfection may be a major contributor to the overall rate of tuberculosis in adults.
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ACKNOWLEDGMENTS |
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We thank Bianca Ghisi for computer counseling, Stefano Rusconi for valuable help, Elizabeth Kaplan and Alan Michael Rosen for professional language assistance, and Mauro Moroni for helpful discussion.
This work was supported by a grant from the Italian National Institute of Health, 2nd National Tuberculosis Project.
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FOOTNOTES |
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* Corresponding author. Mailing address: Institute of Infectious Diseases and Tropical Medicine, "L. Sacco" Hospital, University of Milan, via G. B. Grassi 74, 20157 Milan, Italy. Phone: 39 02 39042676. Fax: 39 02 3560805. E-mail: andrea.gori{at}unimi.it.
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REFERENCES |
|---|
|
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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|---|
| 1. | Ackah, A. N., D. Coulibaly, H. Digbeu, K. Diallo, K. M. Vetter, I. M. Coulibaly, A. E. Greenberg, and K. M. De Cock. 1995. Response to treatment, mortality, and CD4 lymphocyte counts in HIV-infected persons with tuberculosis in Abidjan, Cote d'Ivoire. Lancet 345:607-610[CrossRef][Medline]. |
| 2. | Canetti, G., I. Sutherland, and E. Svandova. 1972. Endogenous reactivation and exogenous reinfection: their relative importance with regard to the development of non-primary tuberculosis. Bull. Int. Union Tuberc. 47:116-134[Medline]. |
| 3. | Chaves, F., F. Dronda, M. Alonso-Sanz, and A. R. Noriega. 1999. Evidence of exogenous reinfection and mixed infection with more than one strain of Mycobacterium tuberculosis among Spanish HIV-infected inmates. AIDS 13:615-620[CrossRef][Medline]. |
| 4. | Codecasa, L. R., A. D. Porretta, A. Gori, F. Franzetti, A. Degli Esposti, A. Lizioli, V. Carreri, M. C. Di Proietto, F. Perozziello, and G. Besozzi. 1999. Tuberculosis among immigrants from developing countries in the province of Milan, 1993-1996. Int. J. Tuberc. Lung Dis. 3:589-595[Medline]. |
| 5. | Connolly, C., A. Reid, G. Davies, W. Sturm, K. P. McAdam, and D. Wilkinson. 1999. Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa. AIDS 13:1543-1547[CrossRef][Medline]. |
| 6. | Daley, C. L., P. M. Small, G. F. Schecter, G. K. Schoolnik, R. A. McAdam, W. R. Jacobs, Jr., and P. C. Hopewell. 1992. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus: an analysis using restriction-fragment-length polymorphisms. N. Engl. J. Med. 326:231-235[Abstract]. |
| 7. | Das, S., S. L. Chan, B. W. Allen, D. A. Mitchison, and D. B. Lawrie. 1993. Application of DNA fingerprinting with IS986 to sequential mycobacterial isolates obtained from pulmonary tuberculosis patients in Hong Kong before, during and after short-course chemotherapy. Tuber. Lung Dis. 74:48-51. |
| 8. |
Fine, P. E. M., and P. M. Small.
1999.
Exogenous reinfection in tuberculosis.
N. Engl. J. Med.
341:1226-1227 |
| 9. | Franzetti, F., A. Gori, E. Iemoli, P. Meraviglia, F. Mainini, T. Quirino, A. degli Esposti, M. degl'Innocenti, A. Grassini, G. Nardi, and A. Cargnel. 1999. Outcome of multidrug-resistant tuberculosis in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 29:553-560[Medline]. |
| 10. | Gori, A., G. Marchetti, L. Catozzi, C. Nigro, G. Ferrario, M. C. Rossi, A. Degli Esposti, A. Orani, and F. Franzetti. 1998. Molecular epidemiology characterization of a multidrug-resistant Mycobacterium bovis outbreak among HIV-positive patients. AIDS 12:445-446[Medline]. |
| 11. |
Horn, D. L.,
D. Hewlett Jr,
W. H. Haas,
W. R. Butler,
C. Alfalla,
E. Tan,
A. Levine,
A. Nayak, and S. M. Opal.
1994.
Superinfection with rifampin-isoniazid-streptomycin-ethambutol (RISE)-resistant tuberculosis in three patients with AIDS: confirmation by polymerase chain reaction fingerprinting.
Ann. Intern. Med.
121:115-116 |
| 12. | Johnson, J., A. Okwera, M. J. Vjecha, F. Byekwaso, J. Nakibali, S. Nyole, J. Milberg, T. Aisu, C. C. Whalen, R. D. Mugerwa, and J. J. Elner. 1997. Risk factors for relapse in human immunodeficiency virus type 1-infected adults with pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 1:446-453[Medline]. |
| 13. | Kamerbeek, J., L. Schouls, A. Kolk, M. van Agterveld, D. van Soolingen, S. Kuijper, A. Bunschoten, H. Molhuizen, R. Shaw, M. Goyal, and J. van Embden. 1997. Simultaneous detection and strain differentation of Mycobacterium tuberculosis for diagnosis and epidemiology. J. Clin. Microbiol. 35:907-914[Abstract]. |
| 14. | Moro, M. L., A. Gori, I. Errante, A. Infuso, F. Franzetti, L. Sodano, E. Iemoli, and the Italian Multidrug-Resistant Tuberculosis Outbreak Study Group. 1998. An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy. AIDS 12:1095-1102[CrossRef][Medline]. |
| 15. |
Murray, J.,
P. Sonnenberg,
S. C. Shearer, and P. Godfrey-Faussett.
1999.
Human immunodeficiency virus and the outcome of treatment for new and recurrent pulmonary tuberculosis in African patients.
Am. J. Respir. Crit. Care Med.
159:733-740 |
| 16. | Nardell, E., B. McInnis, B. Thomas, and S. Weidhaas. 1986. Exogenous reinfection with tuberculosis in a shelter for the homeless. N. Engl. J. Med. 315:1570-1575[Abstract]. |
| 17. |
Nunn, P. P.,
A. M. Elliott, and K. P. McAdam.
1994.
Tropical respiratory medicine. 2. Impact of human immunodeficiency virus on tuberculosis in developing countries.
Thorax
49:511-518 |
| 18. |
Pulido, F.,
J. M. Pena,
R. Rubio,
S. Moreno,
J. Gonzalez,
C. Guijarro,
J. R. Costa, and J. J. Vazquez.
1997.
Relapse of tuberculosis after treatment in human immunodeficiency virus-infected patients.
Arch. Intern. Med.
157:227-232 |
| 19. | Romeyn, J. A. 1970. Exogenous reinfection in tuberculosis. Am. Rev. Respir. Dis. 101:923-927[Medline]. |
| 20. | Sahadevan, R., S. Narayanan, C. N. Paramasivan, R. Prabhakar, and P. R. Narayanan. 1995. Restriction fragment length polymorphism typing of clinical isolates of Mycobacterium tuberculosis from patients with pulmonary tuberculosis in Madras, India, by use of direct-repeat probe. J. Clin. Microbiol. 33:3037-3039[Abstract]. |
| 21. |
Small, P. M.,
R. W. Shafer,
P. C. Hopewell,
S. P. Singh,
M. J. Murphy,
E. Desmond,
M. F. Sierra, and G. K. Schoolnik.
1993.
Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection.
N. Engl. J. Med.
328:1137-1144 |
| 22. |
Sola, C.,
L. Horgen,
J. Maisetti,
A. Devallois,
K. S. Goh, and N. Rastogi.
1998.
Spoligotyping followed by double-repetitive-element PCR as rapid alternative to IS6110 fingerprinting for epidemiological studies of tuberculosis.
J. Clin. Microbiol.
36:1122-1124 |
| 23. |
van Embden, J. D.,
M. D. Cave,
J. T. Crawford, et al.
1993.
Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology.
J. Clin. Microbiol.
31:406-409 |
| 24. |
van Rie, A.,
R. Warren,
M. Richardson,
T. C. Victor,
R. P. Gie,
D. A. Enarson,
N. Beyers, and P. D. van Helden.
1999.
Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment.
N. Engl. J. Med.
341:1174-1179 |
| 25. |
van Soolingen, D.,
P. W. M. Hermans,
P. E. W. de Haas,
D. R. Soll, and J. D. van Embden.
1991.
Occurence 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.
29:2578-2586 |
| 26. | Vynnycky, E., and P. E. M. Fine. 1997. The natural history of tuberculosis: the implications of age-dependent risks of disease and the role of reinfection. Epidemiol. Infect. 119:183-201[CrossRef][Medline]. |
| 27. | Whalen, C., A. Okwera, J. Johnson, M. Vjecha, D. Hom, R. Wallis, R. Huebner, R. Mugerwa, and J. Ellner. 1996. Predictors of survival in human immunodeficiency virus-infected patients with pulmonary tuberculosis. The Makerere University-Case Western Reserve University Research Collaboration. Am. J. Respir. Crit. Care Med. 153:1977-1981[Abstract]. |
Journal of Clinical Microbiology, June 2001, p. 2213-2218, Vol. 39, No. 6
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.6.2213-2218.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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171: 1430-1435
[Abstract] [Full Text] -
Jasmer, R. M., Bozeman, L., Schwartzman, K., Cave, M. D., Saukkonen, J. J., Metchock, B., Khan, A., Burman, W. J., the Tuberculosis Trials Consortium,
(2004). Recurrent Tuberculosis in the United States and Canada: Relapse or Reinfection?. Am. J. Respir. Crit. Care Med.
170: 1360-1366
[Abstract] [Full Text] -
McNabb, S. J. N., Kammerer, J. S., Hickey, A. C., Braden, C. R., Shang, N., Rosenblum, L. S., Navin, T. R.
(2004). Added Epidemiologic Value to Tuberculosis Prevention and Control of the Investigation of Clustered Genotypes of Mycobacterium tuberculosis Isolates. Am J Epidemiol
160: 589-597
[Abstract] [Full Text] -
Garcia de Viedma, D., Marin, M., Ruiz, M. J., Bouza, E.
(2004). Analysis of Clonal Composition of Mycobacterium tuberculosis Isolates in Primary Infections in Children. J. Clin. Microbiol.
42: 3415-3418
[Abstract] [Full Text] -
Milan, S. J., Hauge, K. A., Kurepina, N. E., Lofy, K. H., Goldberg, S. V., Narita, M., Nolan, C. M., McElroy, P. D., Kreiswirth, B. N., Cangelosi, G. A.
(2004). Expanded Geographical Distribution of the N Family of Mycobacterium tuberculosis Strains within the United States. J. Clin. Microbiol.
42: 1064-1068
[Abstract] [Full Text] -
Seidler, A, Nienhaus, A, Diel, R
(2004). The transmission of tuberculosis in the light of new molecular biological approaches. Occup. Environ. Med.
61: 96-102
[Abstract] [Full Text] -
Barnes, P. F., Cave, M. D.
(2003). Molecular Epidemiology of Tuberculosis. NEJM
349: 1149-1156
[Full Text] -
Dahle, U. R., Sandven, P., Heldal, E., Caugant, D. A.
(2003). Continued Low Rates of Transmission of Mycobacterium tuberculosis in Norway. J. Clin. Microbiol.
41: 2968-2973
[Abstract] [Full Text]
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