Publications by authors named "Einar Heldal"

34 Publications

Extending contact screening within a 50-m radius of an index tuberculosis patient using Xpert MTB/RIF in urban Pakistan: Did it impact treatment outcomes?

Int J Infect Dis 2021 Mar 27;104:634-640. Epub 2021 Jan 27.

Centre for Operational Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; Yenepoya Medical College, Yenepoya (deemed to be University), Mangaluru, India.

Background: Pakistan implemented initiatives to detect tuberculosis (TB) patients through extended contact screening (ECS); it improved case detection but treatment outcomes need assessment.

Objectives: To compare treatment outcomes of pulmonary TB (PTB) patients detected by ECS with those detected by routine passive case finding (PCF).

Methods: A cohort study using secondary program data conducted in Lahore, Faisalabad and Rawalpindi districts and Islamabad in 2013-15. We used log binomial regression models to assess if ECS was associated with unfavorable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) after adjusting for potential confounders.

Results: We included 79,431 people with PTB; 4604 (5.8%) were detected by ECS with 4052 (88%) bacteriologically confirmed. In all PTB patients the proportion with unfavorable outcomes was not significantly different in ECS group (9.6%) compared to PCF (9.9%), however, among bacteriologically confirmed patients unfavorable outcomes were significantly lower in ECS (9.9%) than PCF group (11.6%, P = 0.001). ECS was associated with a lower risk of unfavorable outcomes (adjusted relative risk (aRR) 0.90; 95% CI 0.82-0.99) among 'all PTB' patients and bacteriologically confirmed PTB patients (aRR 0.91; 95% CI 0.82-1.00).

Conclusion: In PTB patients detected by ECS the treatment outcomes were not inferior to those detected by PCF.
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http://dx.doi.org/10.1016/j.ijid.2021.01.054DOI Listing
March 2021

Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture-A NOREPOS Population-Based Cohort Study.

J Bone Miner Res 2020 12 26;35(12):2327-2334. Epub 2020 Aug 26.

Norwegian Institute of Public Health, Oslo, Norway.

Immune-mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variations in immune responses affect fracture risk on a population level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post-vaccination skin test response that involves some of the immune pathways that also drive bone loss. From 1963 to 1975, the vast majority of the Norwegian adult population was examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940 to 1960 and aged 14 to 30 years at examination) who had all received Bacille Calmette-Guerin (BCG) vaccination after a negative TST at least 1 year prior and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244,607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway from 1994 to 2013. There were 3517 incident hip fractures during follow-up. Using a predefined Cox model, we found that men with a positive or a strong positive TST result had a 20% (hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01-1.44) and 24% (HR = 1.24, 95% CI 1.03-1.49) increased risk of hip fracture, respectively, compared with men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample and similarly revealed a non-significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response after vaccination is associated with an increased risk of hip fracture decades later among men, possibly because of increased immune-mediated bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4135DOI Listing
December 2020

Diagnosis and treatment of patients with pulmonary nontuberculous mycobacterial diseases in Arkhangelsk, Russia.

Infect Genet Evol 2019 09 1;73:358-361. Epub 2019 Jun 1.

Northern State Medical University, Arkhangelsk, Russian Federation.

Background: Nontuberculous mycobacteria (NTM) are acid-fast bacilli (AFB) that can cause disease in human. Patients with NTM pulmonary disease can be falsely diagnosed with pulmonary tuberculosis (TB) due detection of AFB in sputum and similar clinical and chest X-ray picture. Laboratory detection of NTM is complicated and does not always mean presence of the disease, but can be attributed to colonization or sample contamination. Molecular tests, such as Genotype Mycobacterium CM/AS, allow quick and reliable detection of NTM.

Objective: To assess the NTM identification rate, to estimate the incidence of pulmonary NTM disease and to report the treatment outcomes among patients with NTM disease.

Design: Retrospective cohort design.

Results: NTM were detected among 92 (0.98 per 100,000 population) presumptive pulmonary TB patients in Arkhangelsk region in 2010-2017 among who 39 (0.42 per 100,000 population) patients were diagnosed with NTM disease. The most prevalent species found in our study were M. avium (33%) and M.intracellulare (11%). 69% of patients with NTM disease completed their treatment, 15% died, 13% were lost to follow up and 3% failed treatment.

Conclusion: A system of diagnostics and treatment for NTM disease was set up in the Arkhangelsk region in Russia. Average NTM identification rate and incidence of pulmonary NTM disease were 0.98 per 100,000 and 0.42 per 100,000 population accordingly and were lower than reported in other studies. Treatment success rate in our study was 69% encouraging further improvements in diagnostics and treatment of patients with NTM.
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http://dx.doi.org/10.1016/j.meegid.2019.05.022DOI Listing
September 2019

Building sustainable operational research capacity in Pakistan: starting with tuberculosis and expanding to other public health problems.

Glob Health Action 2019 ;12(1):1555215

h International Union Against Tuberculosis and Lung Disease, South-East Asia Regional Office , New Delhi , India.

: For many years, operational research capacity has been a challenge and has remained a low priority for the health sector in Pakistan. Building research capacity for developing a critical mass of researchers in Pakistan was done through Structured Operational Research and Training Initiative (SORT IT) courses in Paris and Asia between 2010 and 2016. : The aim of this paper is to describe the journey of SORT-IT in Pakistan from its inception to progressive expansion and discuss the challenges and ways forward. : The journey began with the training of the Pakistan NTP research team lead in 2010 in an international SORT IT course at Paris. This was followed by training of two team members in Asia SORT IT courses in 2014 and 2015. These three then worked together to conceive and implement the first national Pakistan SORT IT course supported by WHO/TDR and the Global Fund in 2016. This was facilitated by international facilitators and local trained SORT-IT participants from Paris and Asia. This was followed by two further national SORT IT courses in 2017 and 2018. : Between 2010 and 2017, a total of 34 participants from Pakistan had been enrolled in national and international SORT IT courses. Of the 23 participants from completed courses, 18(78%) successfully completed the course. In total 18 papers were submitted and up until June 2018, 15(83%) have been published and 21 institutions in Pakistan involved with operational research as a result of the SORT IT initiative. : The SORT IT course has been an effective way to build operational research capacity at national level and this has resulted in a large number of published papers providing local evidence for decision making on TB and other disease control programmes. The experience from Pakistan should stimulate other countries to adopt the SORT-IT model.
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http://dx.doi.org/10.1080/16549716.2018.1555215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327920PMC
October 2019

Comprehensive care for all individuals with tuberculosis is needed now.

Lancet Glob Health 2019 05 20;7(5):e536-e537. Epub 2019 Mar 20.

International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; Norwegian Institute of Public Health, Oslo, Norway.

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http://dx.doi.org/10.1016/S2214-109X(19)30150-0DOI Listing
May 2019

Immigrant screening for latent tuberculosis infection: numbers needed to test and treat, a Norwegian population-based cohort study.

BMJ Open 2019 01 17;9(1):e023412. Epub 2019 Jan 17.

Department of Tuberculosis, Blood-Borne and Sexually Transmitted Infections, Norwegian Institute of Public Health, Oslo, Norway.

Objectives: To estimate the number needed to screen (NNS) and the number needed to treat (NNT) to prevent one tuberculosis (TB) case in the Norwegian immigrant latent tuberculosis infection (LTBI) screening programme and to explore the effect of delay of LTBI treatment initiation.

Design: Population-based, prospective cohort study.

Participants: Immigrants to Norway.

Outcome: Incident TB.

Methods: We obtained aggregated data on immigration to Norway in 2008-2011 and used data from the Norwegian Surveillance System for Infectious Diseases to assess the number of TB cases arising in this cohort within 5 years after arrival. We calculated the average NNS and NNT for immigrants from the top 10 source countries for TB in Norway and by estimated TB incidence rates in source countries. We explored the sensitivity of these estimates with regard to test performance, treatment efficacy and treatment adherence using an extreme value approach, and assessed the effects of emigration, time to TB diagnosis (to define incident TB) and intervention timing.

Results: NNS and NNT were overall high, with substantial variation. NNT showed numerically stronger negative correlation with TB notification rate in Norway (-0.75 [95% CI -1.00 to -0.44]) than with the WHO incidence rate (IR) (-0.32 [95% CI -0.93 to 0.29]). NNT was affected substantially by emigration and the definition of incident TB. Estimates were lowest for Somali (NNS 99 [70-150], NNT 27 [19-41]) and highest for Thai immigrants (NNS 585 [413-887], NNT 111 [79-116]). Implementing LTBI treatment in immigrants sooner after arrival may improve the effectiveness of the programme.

Conclusion: Using TB notifications in Norway, rather than IR in source countries, would improve targeting of immigrants for LTBI management. However, the overall high NNT is a concern and challenges the scale-up of preventive LTBI treatment for significant public health impact. Better data are urgently needed to monitor and evaluate NNS and NNT in countries implementing LTBI screening.
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http://dx.doi.org/10.1136/bmjopen-2018-023412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340421PMC
January 2019

Treatment outcomes for isoniazid-monoresistant tuberculosis in Peru, 2012-2014.

PLoS One 2018 4;13(12):e0206658. Epub 2018 Dec 4.

TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Resistance to isoniazid is the most common form of drug-resistance in tuberculosis. However only a tiny proportion of TB patients in the world have access to isoniazid drug susceptibility testing-the widely implemented Xpert MTB/RIF technology only tests for resistance to rifampicin. Patients with isoniazid mono resistance that is not identified at baseline are treated with a standard regimen that effectively results in rifampicin mono-therapy during the latter four months of the six month treatment course, exposing remaining viable organisms to a single agent and greatly increasing the risk of development of multi drug-resistant TB. Unusually, Peru has pioneered universal pre-treatment drug susceptibility testing with methods that identify isoniazid resistance and has thus identified a large number of individuals requiring tailored therapy. Since 2010, treatment in Peru for isoniazid-resistant tuberculosis without multidrug-resistant tuberculosis (Hr-TB) has been with a standardized nine-month regimen of levofloxacin, rifampicin, ethambutol and pyrazinamide. The objectives of this study were to evaluate the outcomes of treatment for patients with Hr-TB initiating treatment with this regimen between January 2012 and December 2014 and to determine factors affecting these outcomes.

Methods: Retrospective cross-sectional study; case data were obtained from the national registry of drug-resistant tuberculosis. Patients diagnosed with isoniazid resistant TB without resistance to rifampicin, pyrazinamide, ethambutol and quinolones as determined by either a rapid drug susceptibility testing (DST) (nitrate reductase test, MODS, Genotype MTBDRplus) or by the proportion method were included.

Findings: A total of 947 cases were evaluated (a further 403 without treatment end date were excluded), with treatment success in 77.2% (731 cases), loss to follow-up in 19.7% (186 cases), treatment failure in 1.2% (12 cases), and death in 1.9% (18 cases). Unfavorable outcomes were associated in multivariate analysis with male gender (OR 0.50, 95% CI 0.34-0.72, p<0.05), lack of rapid DST (OR 0.67, 95% CI 0.50-0.91, p = 0.01), additional use of an injectable second-line anti-tuberculous drug (OR 0.46, 95% CI 0.31-0.70, p<0.05), and treatment initiation in 2014 (OR 0.77, 95% CI 0.62-0.94, p = 0.01).

Interpretation: The treatment regimen implemented in Peru for isoniazid resistant TB is effective for TB cure and is not improved by addition of an injectable second-line agent. Access to rapid DST and treatment adherence need to be strengthened to increase favorable results.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279036PMC
April 2019

A 315 mutation alone should not lead to exclusion of isoniazid in treatment of multidrug-resistant tuberculosis.

Authors:
Einar Heldal

Eur Respir J 2017 10 12;50(4). Epub 2017 Oct 12.

Norwegian Institute of Public Health, Oslo, Norway

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http://dx.doi.org/10.1183/13993003.01696-2017DOI Listing
October 2017

Shorter regimens for multidrug-resistant tuberculosis should also be applicable in Europe.

Eur Respir J 2017 06 1;49(6). Epub 2017 Jun 1.

Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.

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http://dx.doi.org/10.1183/13993003.00228-2017DOI Listing
June 2017

Health system factors influencing management of multidrug-resistant tuberculosis in four European Union countries - learning from country experiences.

BMC Public Health 2017 04 19;17(1):334. Epub 2017 Apr 19.

European Centre for Disease Prevention and Control, Tomtebodavagen 11A, S-171 83, Stockholm, Sweden.

Background: In the European Union and European Economic Area only 38% of multidrug-resistant tuberculosis patients notified in 2011 completed treatment successfully at 24 months' evaluation. Socio-economic factors and patient factors such as demographic characteristics, behaviour and attitudes are associated with treatment outcomes. Characteristics of healthcare systems also affect health outcomes. This study was conducted to identify and better understand the contribution of health system components to successful treatment of multidrug-resistant tuberculosis.

Methods: We selected four European Union countries to provide for a broad range of geographical locations and levels of treatment success rates of the multidrug-resistant tuberculosis cohort in 2009. We conducted semi-structured interviews following a conceptual framework with representatives from policy and planning authorities, healthcare providers and civil society organisations. Responses were organised according to the six building blocks of the World Health Organization health systems framework.

Results: In the four included countries, Austria, Bulgaria, Spain, and the United Kingdom, the following healthcare system factors were perceived as key to achieving good treatment results for patients with multidrug-resistant tuberculosis: timely diagnosis of drug-resistant tuberculosis; financial systems that ensure access to a full course of treatment and support for multidrug-resistant tuberculosis patients; patient-centred approaches with strong intersectoral collaboration that address patients' emotional and social needs; motivated and dedicated healthcare workers with sufficient mandate and means to support patients; and cross-border management of multidrug-resistant tuberculosis to secure continuum of care between countries.

Conclusion: We suggest that the following actions may improve the success of treatment for multidrug-resistant tuberculosis patients: deployment of rapid molecular diagnostic tests; development of context-specific treatment guidance and criteria for hospital admission and discharge in the European context; strengthening patient-centred approaches; development of collaborative mechanisms to ensure cross-border care, and development of long-term sustainable financing strategies.
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http://dx.doi.org/10.1186/s12889-017-4216-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395777PMC
April 2017

Contrasting trends of tuberculosis in the cities of San Pedro Sula and Tegucigalpa, Honduras, 2005-2014.

Rev Panam Salud Publica 2016 Jan;39(1):51-59

Objective To 1) describe and compare the trends of tuberculosis (TB) case notification rates (CNRs) and treatment outcomes in the two largest cities in Honduras (San Pedro Sula and Tegucigalpa) for the period 2005-2014 and 2) identify possible related socioeconomic and health sector factors. Methods This retrospective ecological operational research study used aggregated data from the National TB Program (socioeconomic and health sector information and individual data from the 2014 TB case notification report). Results TB CNRs declined steadily over the study period in Tegucigalpa (from 46 to 28 per 100 000 inhabitants) but remained high in San Pedro Sula (decreasing from 89 to 78 per 100 000 inhabitants). Similar trends were observed for smear-positive TB. While presumptive TB cases examined were similar for both cities, in San Pedro Sula the proportions of presumptive cases with a positive smear; (7.7% versus 3.6%) relapses (8.9% versus 4.2%); and patients lost to follow-up (10.9% versus 2.7%) were significantly higher, and the treatment success lower (75.7% versus 87.0%). San Pedro Sula had lower annual income per capita, fewer public sector health workers and facilities, and a higher and increasing homicide index. The 2014 TB case data from San Pedro Sula showed a significantly lower median age and a higher proportion of assembly plant workers, prisoners, drug abusers, and diabetes. Conclusions The TB rate was higher and treatment success lower, and health care resources and socio-demographic indicators less favorable, in San Pedro Sula versus Tegucigalpa. City authorities, the NTP, and the health sector overall should strengthen early case detection, treatment, and infection control, involving both public and private health sectors.
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January 2016

Implementation of the national tuberculosis guidelines on culture and drug sensitivity testing in Guatemala, 2013.

Rev Panam Salud Publica 2016 Jan;39(1):44-50

Objective To assess whether the National Tuberculosis Program (NTP) guidelines for culture and drug sensitivity testing (DST) in Guatemala were successfully implemented, particularly in cases of smear-negative pulmonary tuberculosis (TB) or previously treated TB, by documenting notification rates by department (geographic area), disease type and category, and culture and DST results. Methods This was a cross-sectional, operational research study that merged and linked all patients registered by the NTP and the National Reference Laboratory in 2013, eliminating duplicates. The proportions with culture (for new smear negative pulmonary cases) and culture combined with DST (for previously treated patients) were estimated and analyzed by department. Data were analyzed using EpiData Analysis version 2.2. Results There were 3 074 patients registered with TB (all forms), for a case notification rate of 20/100 000 population. Of these, 2 842 had new TB, of which 2 167 (76%) were smear-positive pulmonary TB (PTB), 385 (14%) were smear-negative PTB, and 290 (10%) were extrapulmonary TB. There were 232 (8%) previously treated cases. Case notification rates (all forms) varied by department from 2-68 per 100 000 population, with the highest rates seen in the southwest and northeast part of Guatemala. Of new TB patients, 136 had a culture performed and 55 had DST of which the results were 33 fully sensitive, 9 monoresistant, 3 polyresistant, and 10 multidrug resistant TB (MDR-TB). Only 21 (5%) of new smear-negative PTB patients had cultures. Of 232 previously treated patients, 54 (23%) had a culture and 47 (20%) had DST, of which 29 were fully sensitive, 7 monoresistant, 2 polyresistant, and 9 MDR-TB. Of 22 departments (including the capital), culture and DST was performed in new smear-negative PTB in 7 departments (32%) and in previously treated TB in 13 departments (59%). Conclusions Despite national guidelines, only 5% of smear-negative PTB cases had a culture and only 20% of previously treated TB had a culture and DST. Several departments did not perform culture or DST. These short comings must be improved if Guatemala is to curtail the spread of drug resistant forms of TB, while striving to eliminate all TB.
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January 2016

Quality of tuberculosis care at different levels of health care in Brazil in 2013.

Rev Panam Salud Publica 2016 Jan;39(1):3-11

Objective To assess 1) the burden and socio-demographic and clinical characteristics of tuberculosis (TB) cases, and 2) the quality of TB care provided to patients who entered and remained within each health care service level (primary, secondary, or tertiary) and those who moved from one level to another, using process and results indicators. Methods This cross-sectional operational research study assessed new smear-positive pulmonary TB cases diagnosed in Brazilian state capitals in 2013 using TB program records and the TB surveillance system. Quality of care was assessed based on process and results indicators including HIV screening, TB contact screening, Directly Observed Treatment (DOT), sputum smear microscopy monitoring, and treatment outcomes. Results There were 12 977 new smear-positive TB cases reported. Of these, 7 964 (61.4%) cases were diagnosed and treated at the primary care level, 1 195 (9.2%) at the secondary level, 1 521 (11.7%) at the tertiary level, and 2 296 (17.7%) at more than one level, with 65% of the latter group moved from the tertiary level to the primary level. The proportion of cases tested for HIV was significantly higher in patients receiving care at the primary level compared to those receiving care at the secondary level (prevalence ratio (PR): 1.17; 95% confidence interval (CI): 1.07-1.28) and those attending more than one service level. Patients attending the tertiary health care level had a 122% higher PR for not doing DOT ("DOT not done") compared to patients at the primary level (PR: 2.22; CI: 2.12-2.32). When the two levels were compared, the prevalence for an unfavorable outcome (lost to follow-up, death from TB, death with TB, transferred out, or not evaluated) was higher at the tertiary health care level. Conclusions Primary health services are successfully incorporating the management of new smear-positive TB cases. Primary health care obtained better operational indicators than secondary or tertiary levels.
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January 2016

BCG vaccination: a long-lasting protection against tuberculosis?--Authors' reply.

Lancet Infect Dis 2016 Apr;16(4):408-9

Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

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http://dx.doi.org/10.1016/S1473-3099(16)00134-1DOI Listing
April 2016

Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study.

Lancet Infect Dis 2016 Feb 19;16(2):219-26. Epub 2015 Nov 19.

Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, and Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK.

Background: Little is known about how long the BCG vaccine protects against tuberculosis. We assessed the long-term vaccine effectiveness (VE) in Norwegian-born individuals.

Methods: In this retrospective population-based cohort study, we studied Norwegian-born individuals aged 12-50 years who were tuberculin skin test (TST) negative and eligible for BCG vaccination as part of the last round of Norway's mandatory mass tuberculosis screening and BCG vaccination programme between 1962 and 1975. We excluded individuals who had tuberculosis before or in the year of screening and those with unknown TST and BCG status. We obtained TST and BCG information and linked it to the National Tuberculosis Register, population and housing censuses, and the population register for emigrations and deaths. We followed individuals up to their first tuberculosis episode, emigration, death, or Dec 31, 2011. We used Cox regressions to estimate VE against all tuberculosis and just pulmonary tuberculosis by time since vaccination, adjusted for age, time, county-level tuberculosis rates, and demographic and socioeconomic indicators.

Findings: Median follow-up was 41 years (IQR 32-49) for 83 421 BCG-unvaccinated and 44 years (41-46) for 297 905 vaccinated individuals, with 260 tuberculosis episodes. Tuberculosis rates were 3·3 per 100 000 person-years in unvaccinated and 1·3 per 100 000 person-years in vaccinated individuals. The adjusted average VE during 40 year follow-up was 49% (95% CI 26-65), although after 20 years, the VE was not significant (up to 9 years VE [excluding tuberculosis episodes in the first 2 years] 61% [95% CI 24-80]; 10-19 years 58% [27-76]; 20-29 years 38% [-32 to 71]; 30-40 years 42% [-24 to 73]). VE against pulmonary tuberculosis up to 9 years (excluding tuberculosis episodes in the first 2 years) was 67% (95% CI 27-85), 10-19 years was 63% (32-80), 20-29 years was 50% (-19 to 79), and 30-40 years was 40% (-46 to 76).

Interpretation: Findings are consistent with long-lasting BCG protection, but waning of VE with time. The vaccine could be more cost effective than has been previously estimated

Funding: Norwegian Institute of Public Health and London School of Hygiene & Tropical Medicine.
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http://dx.doi.org/10.1016/S1473-3099(15)00400-4DOI Listing
February 2016

Intensified tuberculosis case finding among malnourished children in nutritional rehabilitation centres of Karnataka, India: missed opportunities.

PLoS One 2013 16;8(12):e84255. Epub 2013 Dec 16.

Operational Research Unit (LUXOR), Medecins sans Frontieres, Brussels-Luxembourg.

Background: Severe acute malnutrition (SAM) is the most serious form of malnutrition affecting children under-five and is associated with many infectious diseases including Tuberculosis (TB). In India, nutritional rehabilitation centres (NRCs) have been recently established for the management of SAM including TB. The National TB Programme (NTP) in India has introduced a revised algorithm for diagnosing paediatric TB. We aimed to examine whether NRCs adhered to these guidelines in diagnosing TB among SAM children.

Methods: A cross-sectional study involving review of records of all SAM children identified by health workers during 2012 in six tehsils (sub-districts) with NRCs (population: 1.8 million) of Karnataka, India.

Results: Of 1927 identified SAM children, 1632 (85%) reached NRCs. Of them, 1173 (72%) were evaluated for TB and 19(2%) were diagnosed as TB. Of 1173, diagnostic algorithm was followed in 460 (37%). Among remaining 763 not evaluated as per algorithm, tuberculin skin test alone was conducted in 307 (41%), chest radiography alone in 99 (13%) and no investigations in 337 (45%). The yield of TB was higher among children evaluated as per algorithm (4%) as compared to those who were not (0.3%) (OR: 15.3 [95%CI: 3.5-66.3]). Several operational challenges including non-availability of a full-time paediatrician, non-functioning X-ray machine due to frequent power cuts, use of tuberculin with suboptimal strength and difficulties in adhering to a complex diagnostic algorithm were observed.

Conclusion: This study showed that TB screening in NRCs was sub-optimal in Karnataka. Some children did not reach the NRC, while many of those who did were either not or sub-optimally evaluated for TB. This study pointed to a number of operational issues that need to be addressed if this collaborative strategy is to identify more TB cases amongst malnourished children in India.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084255PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865256PMC
September 2014

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

Eur Respir J 2012 Nov 31;40(5):1081-90. Epub 2012 May 31.

World Health Organization, Regional Office for Europe, Copenhagen, Denmark.

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).
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http://dx.doi.org/10.1183/09031936.00053012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485571PMC
November 2012

The role of entry screening in case finding of tuberculosis among asylum seekers in Norway.

BMC Public Health 2010 Nov 4;10:670. Epub 2010 Nov 4.

Department of Public Health and General Practice, Norwegian University of Science and Technology, MTFS, NO-7491 Trondheim, Norway.

Background: Most new cases of active tuberculosis in Norway are presently caused by imported strains and not transmission within the country. Screening for tuberculosis with a Mantoux test of everybody and a chest X-ray of those above 15 years of age is compulsory on arrival for asylum seekers.We aimed to assess the effectiveness of entry screening of a cohort of asylum seekers. Cases detected by screening were compared with cases detected later. Further we have characterized cases with active tuberculosis.

Methods: All asylum seekers who arrived at the National Reception Centre between January 2005--June 2006 with an abnormal chest X-ray or a Mantoux test ≥ 6 mm were included in the study and followed through the health care system. They were matched with the National Tuberculosis Register by the end of May 2008.Cases reported within two months after arrival were defined as being detected by screening.

Results: Of 4643 eligible asylum seekers, 2237 were included in the study. Altogether 2077 persons had a Mantoux ≥ 6 mm and 314 had an abnormal chest X-ray. Of 28 cases with tuberculosis, 15 were detected by screening, and 13 at 4-27 months after arrival. Abnormal X-rays on arrival were more prevalent among those detected by screening. Female gender and Somalian origin increased the risk for active TB.

Conclusion: In spite of an imperfect follow-up of screening results, a reasonable number of TB cases was identified by the programme, with a predominance of pulmonary TB.
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http://dx.doi.org/10.1186/1471-2458-10-670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991295PMC
November 2010

Tuberculosis on the move.

Lancet 2010 Jun 18;375(9732):2127-9. Epub 2010 May 18.

Division of Infectious Diseases, Emory University, Atlanta, GA 30303, USA.

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http://dx.doi.org/10.1016/S0140-6736(10)60574-0DOI Listing
June 2010

Screening and treatment of latent tuberculosis in a cohort of asylum seekers in Norway.

Scand J Public Health 2010 May 13;38(3):275-82. Epub 2009 Nov 13.

Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

Aims: Asylum seekers are screened for tuberculosis at entry to Norway. We aimed to assess follow-up of screening results at different healthcare levels in relation to demographics, screening results and organizational factors, and how this influenced treatment of latent tuberculosis.

Methods: All asylum seekers >or=18 years with a Mantoux test >or=6 mm or positive x-ray findings who arrived at the National Reception Centre from January 2005 to June 2006, were included. Data were collected from public health authorities in the municipality where the asylum seekers had moved, and from internists in case they had been referred to a specialist. Specialists are responsible for treating latent tuberculosis. Individual subjects were matched with the National Tuberculosis Register to which everybody who had started treatment for latent tuberculosis was reported.

Results: Of 4,643 asylum seekers, 2,237 fulfilled the inclusion criteria. By May 2008, 30 persons had started treatment for latent TB, a median of 17 months (range 3-36) after arrival. A Mantoux test >or=15 mm on arrival was significantly associated with treatment. Demographic factors influenced follow-up in primary healthcare while screening results did not. Referral to specialist was related to screening results. Several specialists were reluctant to diagnose and treat latent tuberculosis and to treat persons without a permanent visa in particular.

Conclusions: Just 1% of the study group received treatment for latent tuberculosis and with a long time delay. The reason for this may be organizational factors affecting follow-up and referral and specialists not following current guidelines.
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http://dx.doi.org/10.1177/1403494809353823DOI Listing
May 2010

Tuberculosis screening and follow-up of asylum seekers in Norway: a cohort study.

BMC Public Health 2009 May 14;9:141. Epub 2009 May 14.

Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

Background: About 80% of new tuberculosis cases in Norway occur among immigrants from high incidence countries. On arrival to the country all asylum seekers are screened with Mantoux test and chest x-ray aimed to identify cases of active tuberculosis and, in the case of latent tuberculosis, to offer follow-up or prophylactic treatment.We assessed a national programme for screening, treatment and follow-up of tuberculosis infection and disease in a cohort of asylum seekers.

Methods: Asylum seekers >or= 18 years who arrived at the National Reception Centre from January 2005 to June 2006, were included as the total cohort. Those with a Mantoux test >or= 6 mm or positive x-ray findings were included in a study group for follow-up.Data were collected from public health authorities in the municipality to where the asylum seekers had moved, and from hospital based internists in case they had been referred to specialist care.Individual subjects included in the study group were matched with the Norwegian National Tuberculosis Register which receive reports of everybody diagnosed with active tuberculosis, or who had started treatment for latent tuberculosis.

Results: The total cohort included 4643 adult asylum seekers and 97.5% had a valid Mantoux test. At least one inclusion criterion was fulfilled by 2237 persons. By end 2007 municipal public health authorities had assessed 758 (34%) of them. Altogether 328 persons had been seen by an internist. Of 314 individuals with positive x-rays, 194 (62%) had seen an internist, while 86 of 568 with Mantoux >or= 15, but negative x-rays (16%) were also seen by an internist. By December 31st 2006, 23 patients were diagnosed with tuberculosis (prevalence 1028/100 000) and another 11 were treated for latent infection.

Conclusion: The coverage of screening was satisfactory, but fewer subjects than could have been expected from the national guidelines were followed up in the community and referred to an internist. To improve follow-up of screening results, a simplification of organisation and guidelines, introduction of quality assurance systems, and better coordination between authorities and between different levels of health care are all required.
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http://dx.doi.org/10.1186/1471-2458-9-141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689201PMC
May 2009

[Drug resistance in tuberculosis].

Tidsskr Nor Laegeforen 2008 Nov;128(22):2588-92

Avdeling for infeksjonsovervåking, Nasjonalt folkehelseinstitutt, Postboks 4404 Nydalen, 0403 Oslo.

Background: The emergence of drug-resistant tuberculosis is one of the main challenges in the global combat against tuberculosis. The objective of the article is to discuss the main causes for emergence of drug resistance, describe the epidemiology of drug-resistant tuberculosis with focus on the situation in Norway and advise on how this should be managed.

Material And Method: This review is based on relevant published literature, data from surveillance of the disease in Norway and current national and international recommendations for prevention and control of tuberculosis.

Results: Tuberculosis can normally be treated effectively with a standardized combination of drugs for six months. The long duration of treatment is a challenge and incorrect treatment causes development of resistant tuberculosis. The objectives of tuberculosis treatment are to cure the patient, to stop transmission of the bacteria and prevent emergence of drug resistance. The total number of patients diagnosed with multidrug resistant tuberculosis (MDR)-TB in Norway is low, although a threefold increase has occurred in the last decade compared to in previous decades. Most patients were born abroad. Treatment of MDR-TB takes up to two years, is costly and has more side effects. Treatment of MDR-TB is associated with lower cure rate and higher fatality; although in Norway most cases are cured.

Discussion: The global situation also affects Norway. Early diagnosis of infectious cases and close monitoring of patients under treatment, by direct observation of medication, can prevent new cases of MDR-TB.
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November 2008

School based screening for tuberculosis infection in Norway: comparison of positive tuberculin skin test with interferon-gamma release assay.

BMC Infect Dis 2008 Oct 17;8:140. Epub 2008 Oct 17.

Division of Infectious Disease Control, Norwegian Institute of Public Health, 0403 Oslo, Norway.

Background: In Norway, screening for tuberculosis infection by tuberculin skin test (TST) has been offered for several decades to all children in 9th grade of school, prior to BCG-vaccination. The incidence of tuberculosis in Norway is low and infection with M. tuberculosis is considered rare. QuantiFERONTB Gold (QFT) is a new and specific blood test for tuberculosis infection. So far, there have been few reports of QFT used in screening of predominantly unexposed, healthy, TST-positive children, including first and second generation immigrants. In order to evaluate the current TST screening and BCG-vaccination programme we aimed to (1) measure the prevalence of QFT positivity among TST positive children identified in the school based screening, and (2) measure the association between demographic and clinical risk factors for tuberculosis infection and QFT positivity.

Methods: This cross-sectional multi-centre study was conducted during the school year 2005-6 and the TST positive children were recruited from seven public hospitals covering rural and urban areas in Norway. Participation included a QFT test and a questionnaire regarding demographic and clinical risk factors for latent infection. All positive QFT results were confirmed by re-analysis of the same plasma sample. If the confirmatory test was negative the result was reported as non-conclusive and the participant was offered a new test.

Results: Among 511 TST positive children only 9% (44) had a confirmed positive QFT result. QFT positivity was associated with larger TST induration, origin outside Western countries and known exposure to tuberculosis. Most children (79%) had TST reactions in the range of 6-14 mm; 5% of these were QFT positive. Discrepant results between the tests were common even for TST reactions above 15 mm, as only 22 % had a positive QFT.

Conclusion: The results support the assumption that factors other than tuberculosis infection are widely contributing to positive TST results in this group and indicate the improved specificity of QFT for latent tuberculosis. Our study suggests a very low prevalence of latent tuberculosis infection among 9th grade school children in Norway. The result will inform the discussion in Norway of the usefulness of the current TST screening and BCG-policy.
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http://dx.doi.org/10.1186/1471-2334-8-140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576307PMC
October 2008

Screening for tuberculosis infection among newly arrived asylum seekers: comparison of QuantiFERONTB Gold with tuberculin skin test.

BMC Infect Dis 2008 May 14;8:65. Epub 2008 May 14.

Division of Infectious Disease Epidemiology, Norwegian Institute of Public Health, 0403 Oslo, Norway.

Background: QuantiFERONTB 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.

Methods: The 1000 asylum seekers (age > or = 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.

Results: Among 912 asylum seekers with valid test results, 29% (264) had a positive QFT test whereas 50% (460) tested positive with TST (indurations > or = 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.

Conclusion: By 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 (> or = 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 > or = 15 mm, but different groups will be missed.
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http://dx.doi.org/10.1186/1471-2334-8-65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2405787PMC
May 2008

Impact of immigration on the molecular epidemiology of Mycobacterium tuberculosis in a low-incidence country.

Am J Respir Crit Care Med 2007 Nov 2;176(9):930-5. Epub 2007 Aug 2.

Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.

Rationale: Programs to prevent the incidence rate of tuberculosis (TB) from increasing in many low-incidence countries are challenged by international travel and immigration from high-burden countries.

Objectives: The current study aimed to determine the effect of such immigration on the genetic diversity of Mycobacterium tuberculosis isolates in an entire nation's population during 1994-2005.

Methods: A total of 3,131 patients were notified with TB during the 12-year period. Of these, 2,284 (73%) had TB verified by culture, and isolates from 2,173 (96%) of these were analyzed by IS6110 restriction fragment length polymorphism.

Measurements And Main Results: Only 31% of the included strains were isolated from nonimmigrants, the remaining 69% were isolated from immigrants. Although the incidence increased throughout the period, the genetic diversity remained high. A total of 135 clusters were identified; the percentage of recent disease was reduced among nonimmigrants, and remained stable among the immigrants during the study period. Although 69% of the isolates originated from immigrants from high-incidence countries, the established TB control program in the receiving country was adequate for the prevention of disease transmission. On average per year, only 2 nonimmigrants and 13 immigrants developed disease as a result of infection within the country by imported M. tuberculosis.

Conclusions: Twelve years of M. tuberculosis importation as a result of immigration from high-incidence countries had little influence on the transmission of this pathogen in the receiving low-incidence country. To prevent future increase of transmission of TB, the current control strategies of low-incidence countries are adequate but must be maintained.
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http://dx.doi.org/10.1164/rccm.200702-187OCDOI Listing
November 2007

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

BMC Infect Dis 2006 Feb 24;6:33. Epub 2006 Feb 24.

Norwegian Institute of Public Health, Oslo, Norway.

Background: Delay 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.

Methods: This 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.

Results: Among 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.

Conclusion: A 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.
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http://dx.doi.org/10.1186/1471-2334-6-33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1435913PMC
February 2006