Donor-derived tuberculosis via orthotopic liver transplantation.

We present a case of donor-derived tuberculosis after liver transplantation, in which the donor origin of the Mycobacterium tuberculosis isolate was made most likely by DNA fingerprinting. Screening for latent tuberculosis of transplant donors originating from high endemic areas with an ex-vivo interferon-gamma release assay should be considered.

Added value of interferon-gamma release assays in screening for tuberculous infection in the Netherlands.

BACKGROUND: Interferon-gamma release assays (IGRAs) are reported to be more specific for the diagnosis of latent tuberculous infection (LTBI) than the tuberculin skin test (TST). The two-step procedure, TST followed by an IGRA, is reported to be cost-effective in high-income countries, but it requires more financial resources. OBJECTIVE: To assess the added value of IGRA compared to TST alone in the Netherlands. METHODS: Test results and background data on persons tested with an IGRA were recorded by the Public Municipal Health Services in a web-based database. The number of persons diagnosed with LTBI using different screening algorithms was calculated. RESULTS: In those tested with an IGRA, at least 60% of persons who would have been diagnosed with LTBI based on TST alone had a negative IGRA. Among those with a TST reaction below the cut-off for the diagnosis of LTBI, 13% had a positive IGRA. For 41% of persons tested with an IGRA after TST, the IGRA influenced whether or not an LTBI diagnosis would be made. CONCLUSION: With the IGRA as reference standard, a high proportion of persons in low-prevalence settings are treated unnecessarily for LTBI if tested with TST alone, while a small proportion eligible for preventive treatment are missed. Incremental costs of the two-step strategy seem to be balanced by the improved targeting of preventive treatment.

Risk of travelling to the country of origin for tuberculosis among immigrants living in a low-incidence country.

SETTING: Two thirds of tuberculosis (TB) patients in the Netherlands are foreign-born. OBJECTIVE: To determine if travelling to the country of origin is a risk factor for TB among two different immigrant groups that have lived in the Netherlands for at least 2 years. DESIGN: In this unmatched case-control study, the frequency and duration of travel to the country of origin in the preceding 12 months were compared between adult Moroccan and Turkish TB patients and community controls. RESULTS: Moroccan patients had travelled more often (26/32 = 81%) in the preceding year than Moroccan controls (472/816 = 58%). The travel-associated odds ratio (OR) for TB among Moroccans was 3.2 (95%CI 1.3-7.7), and increased to 17.2 (95%CI 3.7-79) when the cumulative duration of travel exceeded 3 months. The corresponding population fraction of Moroccan TB cases attributable to recent travel was 56% (95%CI 19-71). Among Turkish immigrants TB was not associated with travel (OR 0.9, 95%CI 0.3-2.4). CONCLUSION: Travel to the country of origin was a risk factor for TB among Moroccans, but not among Turkish people living in the Netherlands. The difference in travel-associated OR between these two immigrant groups is probably related to differences in TB incidence in these countries.

Predictive value for progression to tuberculosis by IGRA and TST in immigrant contacts.

The authors determined the positive predictive value (PPV) for progression to tuberculosis (TB) of two interferon-gamma release assays (IGRAs), QuantiFERON-TB Gold In-tube (QFT-GIT) and T-SPOT.TB, and the tuberculin skin test (TST) in immigrants contacts. Immigrant close contacts of sputum smear-positive TB patients were included when aged > or =16 yrs and their TST result was > or =5 mm 0 or 3 months after diagnosis of the index patient. Contacts were followed for the next 2 yrs for development of TB disease. Of 339 immigrant contacts with TST > or =5 mm, 324 and 299 had valid results of QFT-GIT and T-SPOT.TB, respectively. Nine contacts developed active TB. One patient had not been tested with TST, while another patient had not been tested with QFT-GIT and T-SPOT.TB. The PPV for progression to TB during this period was 9/288 = 3.1% (95% CI 1.3-5.0%) for TST > or =10 mm, 7/184 = 3.8% (95% CI 1.7-5.9%) for TST > or =15 mm, 5/178 = 2.8% (95% CI 1.0-4.6%) for QFT-GIT and 6/181 = 3.3% (95% CI 1.3-5.3%) for T-SPOT.TB. Sensitivity was 100%, 88%, 63% and 75%, respectively. The predictive values of QFT-GIT, T-SPOT.TB and TST for progression to TB disease among immigrant close contacts were comparable.

Interferon-gamma release assays in immigrant contacts and effect of remote exposure to Mycobacterium tuberculosis.

OBJECTIVE: To assess the association between remote exposure to tuberculosis (TB) and results of the tuberculin skin test (TST), and two interferon-gamma release assays (IGRAs)-QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB-in immigrant contacts of sputum smear-positive TB patients. METHODS: Immigrants aged >or=16 years in close contact with smear-positive TB patients were included. QFT-GIT and T-SPOT.TB were performed if the TST induration size was >or=5 mm. Associations between test results and origin from an endemic country were assessed. RESULTS: Of 433 close contacts, 322 (74%) had TST >or=5 mm, of whom, 282 (88%) had valid test results for all assays. Positive QFT-GIT results were obtained for 152/282 (54%) and positive T-SPOT.TB for 168/282 (60%). After adjustment for age, sex and recent contact, positive IGRA results and TST results >/=10 mm were found to be more frequent among immigrants who originated from Africa, in particular sub-Saharan Africa. CONCLUSION: When IGRAs are used to determine latent TB infection in foreign-born individuals, positive findings not only relate to recent TB infection, but also reflect prior TB exposure in the country of origin. This late reactivity will limit their usefulness in contact investigations among immigrants originating from endemic areas.

Tuberculin skin test reactions by time of reading among Dutch travellers.

SETTING: Five travel and TB control clinics in The Netherlands. OBJECTIVE: To assess the variation of skin test reactions between different days of reading. DESIGN: Cohort study of non-BCG-vaccinated travellers. Mantoux skin test data were analysed for associations between time interval between administration and reading and reaction size. RESULTS: There were no significant differences in reaction size to 1 TU PPD between readings at day 3 or 4, either for pre-travel (n = 1004) or post-travel (n = 577) tests, before (P = 0.990 and 0.210, respectively) or after exclusion of 0 mm reactions (P = 0.330 and 0.474). Time intervals were not different for reaction sizes of 0, 1-9 or > or = 10 mm (P = 0.826 and 0.306). There were also no significant associations for simultaneous tests with a sensitin of Mycobacterium scrofulaceum. CONCLUSIONS: Tuberculin skin tests can be read on day 3 or 4, without compromising their validity.

Association of tuberculin sensitivity in Dutch adults with history of travel to areas of with a high incidence of tuberculosis.

International travel may be a source of introduction of tuberculosis into low-incidence countries. We assessed whether, in The Netherlands, sensitivity to tuberculin was associated with a history of travel to countries with a high incidence of tuberculosis. Immunocompetent adults with no history of Bacille Calmette-Guérin vaccination or sensitivity to tuberculin were skin-tested simultaneously with 1-tuberculin unit (TU) purified protein derivative (PPD) of Mycobacterium tuberculosis and 1-TU sensitin of Mycobacterium scrofulaceum. Tuberculin sensitivity was defined as a reaction to PPD of > or =10 mm that was > or =3 mm larger than the reaction to M. scrofulaceum sensitin. Tuberculin sensitivity was found in 7 (0.7%) of 1014 participants (95% confidence interval [CI], 0.3%-1.4%); it was independently associated with a cumulative history of >3-months' travel to high-incidence areas (odds ratio, 6.0; 95% CI, 1.2-31.2; P=.016) and increased in association with total duration of travel (P=.02). Travel to high-incidence areas increases the risk of tuberculin sensitivity and, consequently, of latent tuberculous infection. In countries with a low incidence of tuberculosis, cases of infection acquired during travel may account for a substantial proportion of new infections in the resident population.

Risk of infection with Mycobacterium tuberculosis in travellers to areas of high tuberculosis endemicity.

BACKGROUND: No data exist on risks of infection with Mycobacterium tuberculosis in travellers. We studied incidences of and risk factors for tuberculin skin-test conversion among Dutch long-term travellers to countries of high tuberculosis endemicity. METHODS: In a multicentre, prospective cohort study based in travel and tuberculosis clinics in the Netherlands, 1072 BCG-naive immunocompetent travellers to countries with an estimated annual risk of M. tuberculosis infection of at least 1% were skin tested before departure with 1 tuberculin unit purified protein derivative (PPD) of M. tuberculosis in Tween-80. Those with results less than 2 mm were retested 2-4 months after their return with simultaneous testing for cross-sensitivity to environmental mycobacteria (1 tuberculin unit PPD of M. scrofulaceum in Tween-80). M. tuberculosis infection was defined as a post-travel M. tuberculosis tuberculin skin-test result of at least 10 mm that was 3 mm or more larger than the M. scrofulaceum result. FINDINGS: Post-travel skin-test results were available for 656 (66%) of 988 individuals who were eligible for follow-up. Among these, 12 M. tuberculosis infections were identified (1.8%). The overall incidence rate was 3.5 per 1000 person-months of travel (95% CI 2.0-6.2), and 2.8 per 1000 person-months of travel (1.2-5.5) after exclusion of health-care workers. Two had active tuberculosis at the time of testing (incidence rate 0.6 per 1000 person-months of travel [0.3-2.3]). Work in patient care abroad was an independent risk factor (adjusted rate ratio 5.34, p=0.015). INTERPRETATION: The risk of M. tuberculosis infection in long-term travellers to high-endemicity countries, even if not engaged in health-care work, is substantial and of similar magnitude to the average risk for the local population. BCG vaccination or post-travel tuberculin skin-testing of high-risk travellers should be considered.