Investigation of tuberculosis transmission in Canadian Arctic Inuit communities using DNA fingerprinting.

OBJECTIVE: To understand the transmission of tuberculosis in Inuit communities in the Baffin region of the Canadian Arctic. METHODS: Twenty-one isolates of Mycobacterium tuberculosis from 19 Inuit patients diagnosed with tuberculosis between February 1991 and September 1993 were analyzed by DNA fingerprinting. The DNA fingerprints were achieved by the standard restriction fragment length polymorphism (RFLP) technique, with subsequent probing using the repetitive insertion segment IS6110. RESULTS: The isolates could be divided into three DNA types. The DNA types generally corresponded to the geographic origins of the patients. In most instances only one DNA type of M. tuberculosis was identified in each community. This suggests that a single case was the start of each of the three clusters, most likely due to reactivation. CONCLUSIONS: The results show that molecular typing of M. tuberculosis was useful in determining the mode of transmission of tuberculosis in a remote area of the Canadian Arctic where the disease is endemic. In addition, the information provides useful information for planning interventions in this setting.     

Contact tracing using DNA fingerprinting in an asylum seeker with pulmonary tuberculosis

BACKGROUND: The diagnosis of tuberculosis in asylum seekers is followed by contact tracing, which is routinely performed by the Municipal Health Service (MHS). We investigated cases of tuberculosis whose symptoms became apparent after closure of regular contact tracing. METHODS: Analysis of data from the DNA Fingerprinting Surveillance Project on all Mycobacterium tuberculosis isolates and contact tracing instances. RESULTS: Four additional cases of tuberculosis were detected, caused by bacteria of identical DNA fingerprints. No further contacts with a bacteriologically confirmed form of tuberculosis were found around these four new patients. CONCLUSION: DNA fingerprinting contributed to tracing instances of late manifestations of tuberculosis transmission.     

Association between clustered strain of M. tuberculosis and infectiousness index of tuberculosis cases in a population-based IS6110-RFLP analysis

OBJECTIVE: Isolates of M. tuberculosis were analyzed for their DNA fingerprints to facilitate understanding of ongoing transmission of tuberculosis in Sapporo (population 1.87 million), Japan, where the incidence rate of tuberculosis was 15.0 per 100,000 in 2004. SUBJECT: Out of all tuberculosis patients registered in the city from November 1998 to December 2003, isolates from culture-positive respiratory tuberculosis cases for whom written informed consent had been obtained, were analyzed by restriction fragment length polymorphism (RFLP). The study included 345 cases (249 men and 96 women) whose isolates were available for DNA patterns. METHOD: Using standard IS6110-RFLP typing, cases whose isolates shared identical fingerprints were considered to belong to the same cluster. Proportions of clustered cases were evaluated according to their clinical and socio-economical characteristics. RESULTS: Out of 345 cases, 207 (60.0%) were classified into 59 clusters, and 15% of clustered cases having definite epidemiological links. Multiple logistic regression analysis in men showed that age and infectiousness were significantly related to clustering. The adjusted odds ratios (OR) [95% confidence intervals (CI)] were 0.17 [0.03-0.79] for 30-59 years, 0.15 [0.03-0.69] for 60 years or over and 2.35 [1.17-4.70] for those cases assigned as the highest level of transmission of tuberculosis from the infectiousness index of cases. For women the final model showed the adjusted OR [95% CI] were 0.52 [0.22-1.22] for those with previous history of tuberculosis and 0.33 [0.06-1.85] for diabetics. In male cases with a previous history of tuberculosis, most highly infectious cases were significantly associated with clustering (OR [95% CI], 4.53 [1.16-17.68]). CONCLUSION: The results suggest that highly infectious male tuberculosis cases with endogenous reactivation have contributed to recent transmission of tuberculosis in the studied area.     

A clinic-based molecular epidemiologic study of tuberculosis in Monterrey, Mexico.

SETTING: A tuberculosis clinic associated with a university hospital in Monterrey, Mexico, an urban community with high tuberculosis incidence. OBJECTIVE: To determine the diversity of DNA fingerprint patterns and the extent of drug resistance of Mycobacterium tuberculosis isolates from patients who attended the clinic. DESIGN: Isolates of M. tuberculosis obtained from 186 patients during the period from 31 January 1996 to 31 March 1998 were tested for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin. Demographic data and the social history of each patient were obtained prospectively by interview. The IS6110 DNA fingerprints were obtained for 166 of the 186 isolates. Secondary typing was carried out on isolates with fewer than six copies of IS6110. RESULTS: Thirty-two per cent of the tested isolates (60/ 186) were drug-resistant, and 18% (33/186) were multidrug-resistant. Approximately 55% of the resistant isolates (33/60) were attributed to acquired resistance. A total of 106 different IS6110 fingerprint patterns were observed among the 166 fingerprinted isolates. Based on both IS6110 and pTBN12 fingerprinting, 65 (39%) of the 166 isolates were part of 22 DNA fingerprint clusters. Various drug susceptibility patterns were seen in most clusters. CONCLUSION: Fingerprint clustering indicates extensive recent transmission of tuberculosis in patients attending the clinic. The prevalence of drug-resistant tuberculosis is high.     

Adult-to-child transmission of tuberculosis: household or community contact?

SETTING: If a child develops tuberculosis, it is assumed that the source was an adult infectious case, usually living in the same house. Restriction fragment length polymorphism (RFLP) was used in this study to establish transmission from source cases to children. DESIGN: Adult and child tuberculosis cases were prospectively identified from 1993 to 1998 and cultures of Mycobacterium tuberculosis collected. Interviews and RFLP analysis of M. tuberculosis strains were performed to establish epidemiological links and to confirm household transmission. RESULTS: Tuberculosis was confirmed by culture in 1139 (91%) of 1291 adults and 65 (16%) of 417 children. Due to problems in recovering specimens or extracting DNA, RFLP analysis was done in 832 adults and 35 children: 19 (54%) children had household members identified with tuberculosis, 12 with the same strain as the child. Twenty-nine (83%) strains from children formed part of community clusters, but definite contact with source cases was established in only 15. CONCLUSION: The presence of an adult with infectious tuberculosis in the same house as a child with tuberculosis does not necessarily imply adult-to-child transmission. Young children may be infected in the community or in the household. These findings have implications for contact tracing and treatment strategies in high incidence areas.     

Effect of screening of immigrants on tuberculosis transmission.

SETTING: In The Netherlands all immigrants from highly endemic countries undergo obligatory entry screening by X-ray, followed by voluntary half-yearly screening for 2 years. OBJECTIVE: To estimate the contribution of screening of immigrants to reductions in tuberculosis transmission. DESIGN: All bacteriologically confirmed tuberculosis patients diagnosed between 1994 and 1999 with mycobacterial isolates exhibiting identical DNA fingerprints were assigned to clusters. Clusters were assumed to be a consequence of recent transmission and to have had the first patient as their source case. Among patients with pulmonary tuberculosis from highly endemic countries, the characteristics of source patients were compared with those of non-clustered patients. RESULTS: Of the 1438 selected patients, 187 (13%) were the first in a cluster, 386 (27%) were in a cluster but were not the first case, and 865 (60%) were not clustered. Independent risk factors for being the first in a cluster were young age, nationality, early year of diagnosis, longer duration of treatment and no concurrent extra-pulmonary tuberculosis. In univariate analysis, passively detected patients and patients with a long duration of stay in The Netherlands were more likely to be the first in a cluster than patients detected by screening and recent arrivals, respectively. However, these variables were strongly associated. CONCLUSION: Screening of immigrants can reduce tuberculosis transmission. This effect is in part due to confounding by duration of stay.     

Transmission of tuberculosis in San Francisco and its association with immigration and ethnicity.

OBJECTIVE: To determine tuberculosis transmission dynamics in San Francisco and its association with country of birth and ethnicity. METHODS: Restriction fragment length polymorphism (RFLP) typing was performed on Mycobacterium tuberculosis isolates from culture-positive pulmonary tuberculosis patients in San Francisco (1991 through 1996), using IS6110 as a probe. Patients were assigned to clusters based on mycobacterial isolates with identical DNA fingerprints. Clusters were assumed to have arisen from recent transmission. A transmission index was defined as the average number of culture-positive pulmonary tuberculosis cases generated by a single source case and calculated for subgroups. RESULTS: The transmission index was higher in US-born (0.59) than in foreign-born groups (0.21), and was highest in blacks, in particular those aged under 35 years. The increased transmission index among blacks was not explained by smear-positivity, human immunodeficiency virus infection, or increased susceptibility to disease progression. CONCLUSION: US-born tuberculosis cases generated more secondary cases than immigrants. Young blacks appear to be a high-risk group for tuberculosis transmission. These results suggest the need to develop interventions targeted towards this risk group.     

Estimation of serial interval and incubation period of tuberculosis using DNA fingerprinting.

OBJECTIVE: To determine the frequency distributions of serial interval and incubation period of tuberculosis within 4 years of transmission, and to identify correlates of serial intervals and incubation periods. METHODS: DNA fingerprints were obtained for all isolates from all culture-positive patients notified in The Netherlands from 1993 to 1996. Patient information was obtained from the National Tuberculosis Register. Results from contact investigations were provided by public health services. Source cases and secondary cases of tuberculosis were identified, based on 1) identical DNA fingerprints, and 2) epidemiological confirmation of contact. Under-representation of long intervals were corrected for by weighting cases. RESULTS: A total of 69 source-secondary case couples were identified. The geometric mean serial interval was 29.5 weeks (95% confidence interval [CI] 22.8-38.2 weeks) and the geometric mean incubation period 20.8 weeks (95% CI 15.5-27.8 weeks). Serial intervals and incubation periods tended to increase with age (P > 0.05). Three secondary cases with human immunodeficiency virus infection showed very short incubation periods (P > 0.05). CONCLUSION: Using a new methodology, the distribution of incubation periods of tuberculosis gave results consistent with earlier studies.     

The role of core groups in transmitting Mycobacterium tuberculosis in a high prevalence community in Southern Mexico.

SETTING: A community in Southern Mexico with a high prevalence of tuberculosis. OBJECTIVE: To characterize the transmission dynamics in a region with a DOTS-based tuberculosis control program. DESIGN: Community-based screening of chronic coughers between 1 March 1995 and 31 August 1996. Individuals with acid-fast bacilli (AFB) in their sputum were enrolled, interviewed, and had mycobacterial cultures and fingerprinting performed. In-depth interviews were conducted on all persons with DNA fingerprinting. RESULTS: AFB smears were performed on 1424 individuals, 124 of whom were microbiologically confirmed. Of the 95 cases for whom bacterial DNA fingerprints were available, 38 were in clusters. The largest cluster involved seven individuals who were members of a social network centered on a series of unlicensed bars. CONCLUSION: This population-based molecular epidemiologic study showed that a focus of transmission within a social network accounted for one fourth of transmission which rapidly progressed to disease. These observations raise questions about the potential benefit of targeted tuberculosis control interventions in health jurisdictions approaching WHO-defined DOTS benchmarks.     

A prospective evaluation of the clinical value of nation-wide DNA fingerprinting of tuberculosis isolates in Denmark.

SETTING: Denmark, a country with a low incidence of tuberculosis (TB). OBJECTIVE: To evaluate the value of the nation-wide DNA fingerprinting of Mycobacterium tuberculosis isolates performed in Denmark since 1992. DESIGN: Prospective study of consecutive patients with culture-verified TB from five large TB Departments in Denmark during a 7-month period in 1998. Results of IS6110 RFLP and spoligotyping were compared to those in the nation-wide Danish DNA-fingerprint database which covers approximately 95% of all culture-verified TB cases from 1992 onwards. Questionnaires asking about contact tracing and epidemiological links were sent to the patients' treating physicians. RESULTS: Of the 177 patients included in the study, 57 were Danes, one was from Iceland, 111 were immigrants, and eight were from Greenland. Responses to the questionnaires were obtained from 163 patients (92%). Four cases of unsuspected transmission were detected: one of nosocomial spread of TB, one of occupational acquisition of TB and two of transmission in an international school, leading to further contact tracing among 75 schoolchildren. These four cases were all the result of short-term contacts. In 22 cases, contact with one or more TB patient(s) was reported. In six of these, the DNA-fingerprint result revealed that the presumed contact could not be the source of infection, even though in two of the cases the known TB contact was from the household. CONCLUSION: Nation-wide DNA fingerprinting of TB isolates provides information that could not have been obtained otherwise, and contribute to the understanding of TB transmission in Danish society. In some cases the results lead to further contact tracing. Short-term contact can apparently result in transmission of TB.     

Evidence for local transmission and reactivation of tuberculosis in the Toronto Somali community

To further understand the molecular and clinical epidemiology of tuberculosis in the Toronto Somali community, molecular fingerprinting using IS6110 restriction fragment length polymorphism typing or spoligotyping was performed on M. tuberculosis isolates obtained from Somali-Canadians who developed active disease from 1997 to 2001. Molecular fingerprints were further compared with those obtained from Somalis residing in Denmark. 142 Somali TB patients were reported, for whom, 80 isolates were fingerprinted. 25% of isolates were clustered. Three clusters involving 2 patients each were identified out of the17 isolates that underwent spoligotyping. Of the 63 isolates typed by the IS6110 method, 6 clusters (4 of 2 patients and 2 of 3 patients) were identified. 57% of these isolates were found to be identical to Danish isolates. Our study suggests that a combination of reactivation and recent transmission are responsible for the high incidence rates of tuberculosis in this community. We recommend that ongoing surveillance and treatment programmes be directed towards this community.     

IS6110 DNA fingerprinting analysis of individually separated colonies of Mycobacterium tuberculosis

There are no data so far that show IS6110 restriction fragment length polymorphism (RFLP) patterns of individually separated tuberculosis bacilli from clinical isolates, and their alterations during follow-up surveys. We picked 20-60 tuberculosis clones from clinical isolates under anti-tuberculosis medication, and individually analysed their DNA fingerprinting patterns using IS6110 RFLP as well as spoligotyping as a second typing. The study using cloned bacilli of Mycobacterium tuberculosis showed that clinical isolates contained several clones with different DNA fingerprints and that their band patterns altered weakly but distinctly during follow-up surveys. However, there was no significant difference in the fingerprinting patterns when clinical isolates were to RFLP without separating to subjected/individual colonies. In view of the IS6110 RFLP of individually separated tuberculosis bacilli, we have now speculated several possibilities: (1) that clones with different DNA fingerprints exist in clinical isolates; (2) that IS6110 RFLP patterns of the materials depend on the population of the original clone and the variants having DNA fingerprints different from the original pattern; and (3) that their band patterns are influenced not only by the stability of the original germ having its own fingerprint, but also by the fragility of the new clones.     

Clinical and programmatic mismanagement rather than community outbreak as the cause of chronic, drug-resistant tuberculosis in Buenaventura, Colombia, 1998.

SETTING: Buenaventura, Colombia. OBJECTIVE: To assess whether antituberculosis drug resistance was generated by poor management or community transmission. DESIGN: Treatment-failure and new tuberculosis (TB) patients identified between May 1997 and June 1998 were interviewed and their treatment histories reviewed. Bacteriologic testing, including drug susceptibility profiles (DSP) and DNA fingerprinting by restriction fragment length polymorphism (RFLP), was performed and human immunodeficiency virus (HIV) testing was offered. RESULTS: DSP and RFLP fingerprints were obtained for isolates from 34 of 64 treatment-failure patients; 25 (74%) were resistant to > or = one drug. Fifteen of the 25 patients consented to HIV testing; none were positive. An average of 2.8 major treatment errors per patient was identified. RFLP from the treatment-failure patients revealed 20 unique isolates and six clusters (isolates with identical RFLP); 4/6 clusters contained isolates with different DSP. Analysis of the RFLP from both treatment-failure and new patients revealed that 44/111 (40%) isolates formed 18 clusters. Four of 47 (9%) new patients had multidrug-resistant TB (MDR-TB). Eleven isolates belonged to the Beijing family, related to the MDR strain W. CONCLUSION: Drug resistance in Buenaventura results from both poor management and community transmission. Dependence on DSP to identify TB transmission is inadequate when programmatic mismanagement is common.     

武汉市635例初治涂阳肺结核患者家庭接触者肺结核发病情况分析

搜集2015年1月至2017年12月武汉市肺科医院住院的635例初治涂阳肺结核患者的临床资料,筛查1242名家庭接触者活动性肺结核的检出率。家庭接触者中活动性肺结核检出率为1.69%(21/1242)。家庭接触者中配偶、父母、子女或其他亲属活动性肺结核检出率分别为 1.51%(7/464)、3.66%(9/246)和0.94%(5/532),父母的肺结核检出率最高,差异有统计学意义(χ ²=7.036,P=0.008)。荧光染色分枝杆菌阳性、+、++、+++、++++患者家庭接触者检出率分别为0.60%(2/334)、0.50%(2/401)、1.11%(3/271)、4.32%(6/139)、8.25%(8/97),差异有统计学意义(χ ²=37.232,P=0.000)。初治涂阳肺结核并发气管支气管结核患者的家庭接触者活动性肺结核检出率为3.01%(10/332)。当初治涂阳肺结核患者痰菌量大、并发气管支气管结核,或接触者为患者父母则更易被传染。     

Tuberculosis transmission in the family

OBJECTIVE: To evaluate the risk of tuberculosis (TB) transmission from family members with infectious TB to other family members, and to examine whether household contact investigations had an impact on tuberculosis patterns. DESIGN: Under the direction of the Taipei Municipal Chronic Disease Hospital, 12 full-time public health nurses recruited the household contacts of TB patients. Chest X-ray examination was recommended for adult contacts. Child contacts received the Mantoux tuberculin skin test, and radiography was recommended if the results were positive. SETTING: Family contacts of all TB index patients who attended one of 29 hospitals in Taipei, from July 1993 through June 1996. The medical records of index patients were obtained from the National Tuberculosis Registry. RESULTS: During the study period, the families of 3903 index patients, comprising 11873 contacts, were investigated. Among these, 4595 received radiography, for a response rate of 38.7%. Of these, 284 had active pulmonary disease: 188 (66.3%) had minimal disease, 79 (27.8%) had moderately advanced disease, and only 17 (5.9%) had far advanced disease. Overall, the index patients had more advanced TB: only 1261 (32.3%) had minimal disease, while 2022 (51.8%) had moderately advanced disease and 620 (15.9%) had far advanced disease. CONCLUSIONS: These data show a relatively high risk of intrafamily TB transmission. Our findings also show that family contact investigations may help to diagnose TB in earlier stages. Such an approach should greatly reduce the number of new TB cases and speed eradication of the disease.     

Association of prevalence of tuberculin reactions with closeness of contact among household contacts of new smear-positive pulmonary tuberculosis patients.

OBJECTIVES: Among household contacts of newly diagnosed smear-positive pulmonary tuberculosis (TB) patients, to examine the association of apparent tuberculosis transmission with the closeness and duration of contact. METHODS: Household contacts of newly diagnosed patients with smear-positive pulmonary TB were identified, as well as a healthy population sample. Household contacts were categorized into three groups based on closeness, regularity, and duration of contact with index cases. All subjects underwent tuberculin testing. RESULTS: Among the household contacts, 47 of 112 (42%) of very close/intimate contacts had positive tuberculin tests, compared to 121 of 356 (34%) close/ regular contacts and 23 of 178 (13%) not close/sporadic contacts and 55 of 355 (16%) of a healthy population sample. CONCLUSIONS: Even among household contacts of smear-positive pulmonary TB patients, there were major differences in the proximity and duration of contact which were strongly associated with differences in the prevalence of positive tuberculin reactions.     

Factors associated with the household contact screening adherence of tuberculosis patients

A cross-sectional study was conducted to explore factors associated with the adherence of tuberculosis patients in bringing their household contacts to a TB clinic in Bangkok, Thailand. During the study period, May to December 2003, 325 sputum-smear-positive tuberculosis patients were recruited into the study. Of the 325 eligible tuberculosis patients, 169 (52.00%, 95% Cl = 47.00-57.00) brought their household contacts to the TB clinic. Psychosocial and cues to action factors were examined as indicators of the household contact screening adherence of tuberculosis patients. The results reveal that the household contact screening adherence of tuberculosis patients was significantly associated with a higher perceived susceptibility (Adjusted OR = 2.90, 95% Cl = 1.18-7.16), lower perceived barriers (Adjusted OR = 4.60, 95% CI = 1.99-10.60), a higher intention to bring the contacts to the TB clinic (Adjusted OR = 3.35, 95% Cl = 1.44-7.76), and a short distance from home to the TB clinic (Adjusted OR = 11.47, 95% Cl = 4.57-28.79). The results from this study provide information for TB clinic staff for developing an appropriate intervention program. Through effective intervention and active policy enforcement, a higher percentage of household contact screening adherences can be achieved.     

Infant tuberculosis in Austria—Trend reversal since 1990?

Summary Since 1990 a relatively high number of cases of childhood tuberculosis has been observed in Austria, mainly occurring in the age-group of 0–4 years. Within this group most cases were registered in 1995. Since the beginning of 1995 the establishment of a lab-supported nationwide data collection system enables a more detailed recording of the cases diagnosed. Out of the 85 cases with infant tuberculosis registered in 1995 and 1996, 66 were diagnosed with pulmonary manifestation. In 45 cases tuberculosis was proven by culture. In nine (20%) of these cases the most likely route of infection has appeared to be direct transmission from an adult in the same household suffering from culture proven tuberculosis in the same year. For three of the cases the DNA of the isolatedMycobacterium tuberculosis strains from the adult and the infant was typed using RFLP analysis. In each case identical strains could be demonstrated.