Einar Heldal

Patient and health care system delays in the start of tuberculosis treatment in Norway

BackgroundDelay in start of tuberculosis (TB) treatment has an impact at both the individual level, by increasing the risk of morbidity and mortality, and at the community level, by increasing the risk of transmission. The aims of this study were to assess the delays in the start of treatment for TB patients in Oslo/Akershus region, Norway and to analyze risk factors for the delays.MethodsThis study was based on information from the National TB Registry, clinical case notes from hospitals and referral case notes from primary health care providers. Delays were divided into patient, health care system and total delays. The association with sex, birthplace, site of the disease and age group was analyzed by multiple linear regression.ResultsAmong the 83 TB patients included in this study, 71 (86%) were born abroad. The median patient, health care system and total delays were 28, 33 and 63 days respectively, with a range of 1–434 days. In unadjusted analysis, patient delay and health care system delay did not vary significantly between men and women, according to birthplace or age group. Patients with extra-pulmonary TB had a significantly longer patient, health care system and total delay compared to patients with pulmonary TB. Median total delay was 81 and 56 days in the two groups of TB patients respectively. The health care system delay exceeded the patient delay for those born in Norway. The age group 60+ years had significantly shorter patient delay than the reference group aged 15–29 years when adjusted for multiple covariates. Also, in the multivariate analysis patients born in Norway had significantly longer health care system delay than patients born abroad.ConclusionA high proportion of patients had total delays in start of TB treatment exceeding two months. This study emphasizes the need of awareness of TB in the general population and among health personnel. Extra-pulmonary TB should be considered as a differential diagnosis in unresolved cases, especially for immigrants from high TB prevalence countries.

Minimum package for cross-border TB control and care in the WHO European region: a Wolfheze consensus statement

The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants. A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011. Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country. The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support).

Continued Low Rates of Transmission of Mycobacterium tuberculosis in Norway

ABSTRACT In this study, we determined the genetic diversity of Mycobacterium tuberculosis isolated in Norway from 1999 to 2001. The results were compared to those for strains isolated from 1994 to 1998. A total of 818 patients were diagnosed with tuberculosis (TB) during the last 3-year period. Of these cases, 576 (70%) were verified by culturing, and strains from 551 patients (96%) were analyzed by the IS6110 restriction fragment length polymorphism (RFLP) method. We excluded 13 strains (2.4%) from the analyses, since they were found to represent false-positive samples. A total of 67 strains (12%) that carried fewer than five copies of IS6110 were analyzed by spoligotyping. The strains were from 157 patients (29%) of Norwegian origin and 381 patients (71%) of foreign origin. The rate of diversity among all of the strains was 90%, while in 1994 to 1998 it was 87%. Clusters were assumed to have arisen from recent transmission; the degree of such transmission was 10% in 1999 to 2001, while for the whole 8-year period (1994 to 2001), it was 11%. Of the 109 patients diagnosed as being part of a cluster in 1999 to 2001, 89 were infected with a strain that carried more than four copies of IS6110. Among these 89 patients, 52 (58%) were infected with a strain that had already been identified in 1994 to 1998. The results indicated that most cases of TB in Norway were due to the import of new strains rather than to transmission within the country. This finding demonstrates that screening of immigrants for TB upon arrival in Norway needs to be improved. Outbreaks, however, were caused mainly by strains that have been circulating in Norway for many years.

Tuberculosis screening in migrants in selected European countries shows wide disparities

Well-established tuberculosis screening units in Western Europe were selectively sampled. Three screening units in Norway, two in the UK, one in the Netherlands and one in Switzerland were evaluated. The aim of this study was to describe a range of service models used at a number of individual tuberculosis units for the screening of new entrants into Europe. Semi-structured interviews were conducted with clinicians, nurses and administrators from a selected sample of European tuberculosis screening units. An outline of key themes to be addressed was forwarded to units ahead of scheduled interviews. Themes included the history of the unit, structure, processes and outputs involved in screening new entrants for tuberculosis. Considerable variation in screening services exists in the approaches studied. Units are sited in transit camps or as units within hospital facilities. Staff capacity and administration varies from one clinic per week with few dedicated staff to fully dedicated units. Only one site recorded symptoms; tuberculin testing was universal in children, but varied in adults; chest radiograph screening was universal except at one site where a positive tuberculin skin test or symptoms were required in those <35 yrs of age before ordering a radiograph. Few output data are routinely and systematically collected, which hinders comparison and determination of effectiveness and efficiency. Service models for screening new immigrants for tuberculosis appear to vary in Western Europe. The systematic collection of data would make international comparisons between units easier and help draw conclusions that might usefully inform service development.

Treatment outcome of new culture positive pulmonary tuberculosis in Norway

BackgroundThe key elements in tuberculosis (TB) control are to cure the individual patient, interrupt transmission of TB to others and prevent the tubercle bacilli from becoming drug resistant. Incomplete treatment may result in excretion of bacteria that may also acquire drug resistance and cause increased morbidity and mortality. Treatment outcome results serves as a tool to control the quality of TB treatment provided by the health care system. The aims of this study were to evaluate the treatment outcome for new cases of culture positive pulmonary TB registered in Norway during the period 1996–2002 and to identify factors associated with non-successful treatment.MethodsThis was a register-based cohort study. Treatment outcome was assessed according to sex, birthplace, age group, isoniazid (INH) susceptibility, mode of detection and treatment periods (1996–1997, 1998–1999 and 2000–2002). Logistic regression was also used to estimate the odds ratio for treatment success vs. non-success with 95% confidence interval (CI), taking the above variables into account.ResultsAmong the 655 patients included, the total treatment success rate was 83% (95% CI 80%–86%). The success rates for those born in Norway and abroad were 79% (95% CI 74%–84%) and 86% (95% CI 83%–89%) respectively. There was no difference in success rates by sex and treatment periods. Twenty-two patients (3%) defaulted treatment, 58 (9%) died and 26 (4%) transferred out. The default rate was higher among foreign-born and male patients, whereas almost all who died were born in Norway. The majority of the transferred out group left the country, but seven were expelled from the country. In the multivariate analysis, only high age and initial INH resistance remained as significant risk factors for non-successful treatment.ConclusionAlthough the TB treatment success rate in Norway has increased compared to previous studies and although it has reached a reasonable target for treatment outcome in low-incidence countries, the total success rate for 1996–2002 was still slightly below the WHO target of success rate of 85%. Early diagnosis of TB in elderly patients to reduce the death rate, abstaining from expulsion of patients on treatment and further measures to prevent default could improve the success rate further.

Molecular Epidemiology of Mycobacterium tuberculosis in Norway

ABSTRACT The incidence of tuberculosis in Norway is one of the lowest in the world, and approximately half of the cases occur in first- and second-generation immigrants. In the present study, the genetic diversity of 92% of all strains of Mycobacterium tuberculosis isolated in Norway in 1994 to 1998 was assessed using restriction fragment length polymorphism (RFLP) analysis, with the insertion sequence IS6110 and the repetitive element DR as probes, to determine the degree of active transmission between patients. The DR probe was used as a secondary molecular marker to support or rule out clustering of strains with fewer than five copies of IS6110. After exclusion of 20 cultures representing laboratory contamination, 573 different IS6110 patterns were found among the 698 strains analyzed. Of these 573 patterns, 542 were observed only once and 31 were shared by 2 to 14 isolates. Among 81 strains (11.5%) carrying fewer than five copies of IS6110, 56 RFLP patterns were found when the results of both the IS6110 and DR methods were combined. Among the 698 strains, 570 were considered to be independent cases. A total of 14.5% of the native Norwegians and 19.7% of the foreign patients were part of a cluster. Thus, the degree of recent transmission of tuberculosis in Norway is low and the great majority of the cases are due to reactivation of previous disease. Transmission between immigrants and native Norwegians is uncommon. Two outbreaks, one among native Norwegians and one mainly among immigrants, have been ongoing for several years, indicating that, even in a low-incidence country such as Norway, with a good national program for tuberculosis surveillance, certain transmission chains are difficult to break.

Screening for tuberculosis infection among newly arrived asylum seekers: Comparison of QuantiFERON ® TB Gold with tuberculin skin test

BackgroundQuantiFERON®TB Gold (QFT) is a promising blood test for tuberculosis infection but with few data so far from immigrant screening. The aim of this study was to compare results of QFT and tuberculin skin test (TST) among newly arrived asylum seekers in Norway and to assess the role of QFT in routine diagnostic screening for latent tuberculosis infection.MethodsThe 1000 asylum seekers (age ≥ 18 years) enrolled in the study were voluntarily recruited from 2813 consecutive asylum seekers arriving at the national reception centre from September 2005 to June 2006. Participation included a QFT test and a questionnaire in addition to the mandatory TST and chest X-ray.ResultsAmong 912 asylum seekers with valid test results, 29% (264) had a positive QFT test whereas 50% (460) tested positive with TST (indurations ≥ 6 mm), indicating a high proportion of latent infection within this group. Among the TST positive participants 50% were QFT negative, whereas 7% of the TST negative participants were QFT positive. There was a significant association between increase in size of TST result and the likelihood of being QFT positive. Agreement between the tests was 71–79% depending on the chosen TST cut-off and it was higher for non-vaccinated individuals.ConclusionBy using QFT in routine screening, further follow-up could be avoided in 43% of the asylum seekers who would have been referred if based only on a positive TST (≥ 6 mm). The proportion of individuals referred will be the same whether QFT replaces TST or is used as a supplement to confirm a positive TST, but the number tested will vary greatly. All three screening approaches would identify the same proportion (88–89%) of asylum seekers with a positive QFT and/or a TST ≥ 15 mm, but different groups will be missed.

Deciphering an outbreak of drug-resistant Mycobacterium tuberculosis.

ABSTRACT There have been ample warnings that multidrug-resistant (MDR) tuberculosis (TB) will continue to emerge if countries do not strengthen their control of TB. In low-incidence European countries, however, these warnings have been substantiated mainly by outbreaks in association with human immunodeficiency virus (HIV)-positive patients. The aim of this study was to investigate an outbreak of infection with MDR and drug-resistant Mycobacterium tuberculosis that was diagnosed among 20 HIV-negative patients living in Norway. Of these, 19 were immigrants from East Africa and one was an ethnic Norwegian. We wanted to find out if transmission had taken place in Norway or abroad and to identify the genetic basis of drug resistance. The strains were analyzed by IS6110 restriction fragment length polymorphism, antibiotic susceptibility tests, spoligotyping, reverse hybridization to regions of the rpoB gene, and sequencing of the katG gene. Epidemiological links between the patients were mapped, and the strains were compared to those isolated in 36 other countries and regions. All strains were resistant to isoniazid and carried Ala234Gly, Ser315Thr, and Arg463Leu substitutions in the katG gene. Eleven strains were MDR and carried a Ser531Leu substitution in the rpoB gene. MDR was acquired in the index patient after arrival in Norway. Links were found among 14 patients. The strain was imported from Somalia but acquired MDR and was transmitted in Norway. This demonstrated that MDR strains are not necessarily imported from high-incidence countries and can be highly communicable. The outbreak underscores a deficiency in the TB control measures employed in many countries and challenges the adequacy of the policy of screening immigrants for TB only on arrival.

Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda

Frank Cobelens and colleagues outline key research questions that need to be addressed to maximize the impact of programmatic management of drug-resistant tuberculosis.

Risk factors for recent transmission of Mycobacterium tuberculosis

In recent decades, the decline of tuberculosis has stopped in Western Europe, mainly due to increased immigration from high-prevalence countries. The objective of the current study was to identify risk factors for developing tuberculosis following recent infection, in order to better target interventions. Strains from 861 culture-positive cases, diagnosed in Norway in 1994–1999, were analysed by use of restriction fragment length polymorphism (RFLP). A cluster was defined as two or more isolates with identical RFLP patterns. Risk factors for being part of a cluster were identified by univariate and multivariate analysis. A total of 134 patients were part of a cluster. These constituted 5% Asian-born, 18% Norwegian-born, 24% European-born and 29% African-born patients. Four independent risk factors for being part of a cluster were identified: being born in Norway, being of young age, being infected with an isoniazid-resistant strain and being infected with a multidrug-resistant strain. Transmission of tuberculosis may be further reduced by improving case management, contact tracing, preventive treatment, screening of immigrants and access to health services for the foreign-born population.