SARS-CoV-2 infections and hospitalisations among immigrants in Norway-significance of occupation, household crowding, education, household income and medical risk: a nationwide register study.

BACKGROUND: As in other countries, the COVID-19 pandemic has affected Norway's immigrant population disproportionately, with significantly higher infection rates and hospitalisations. The reasons for this are uncertain. METHODS: Through the national emergency preparedness register, BeredtC19, we have studied laboratory-confirmed infections with SARS-CoV-2 and related hospitalisations in the entire Norwegian population, by birth-country background for the period 15 June 2020 to 31 March 2021, excluding the first wave due to limited test capacity and restrictive test criteria. Straightforward linkage of individual-level data allowed adjustment for demographics, socioeconomic factors (occupation, household crowding, education and household income), and underlying medical risk for severe COVID-19 in regression models. RESULTS: The sample comprised 5.49 million persons, of which 0.91 million were born outside of Norway, there were 82,532 confirmed cases and 3088 hospitalisations. Confirmed infections in this period (per 100,000): foreign-born 3140, Norwegian-born with foreign-born parents 4799 and Norwegian-born with Norwegian-born parent(s) 1011. Hospitalisations (per 100,000): foreign-born 147, Norwegian-born with foreign-born parents 47 and Norwegian-born with Norwegian-born parent(s) 37. The addition of socioeconomic and medical factors to the base model (age, sex, municipality of residence) attenuated excess infection rates by 12.0% and hospitalisations by 3.8% among foreign-born, and 10.9% and 46.2%, respectively, among Norwegian-born with foreign parents, compared to Norwegian-born with Norwegian-born parent(s). CONCLUSIONS: There were large differences in infection rates and hospitalisations by country background, and these do not appear to be fully explained by socioeconomic and medical factors. Our results may have implications for health policy, including the targeting of mitigation strategies.

The correlation between socioeconomic factors and COVID-19 among immigrants in Norway: a register-based study.

AIM: Immigrants in Norway have higher COVID-19 notification and hospitalisation rates than Norwegian-born individuals. The knowledge about the role of socioeconomic factors to explain these differences is limited. We investigate the relationship between socioeconomic indicators at group level and epidemiological data for all notified cases of COVID-19 and related hospitalisations among the 23 largest immigrant groups in Norway. METHODS: We used data on all notified COVID-19 cases in Norway up to 15 November 2020, and associated hospitalisations, from the Norwegian Surveillance System for Communicable Diseases and the emergency preparedness register at the Norwegian Institute of Public Health. We report notified COVID-19 cases and associated hospitalisation rates per 100,000 and their correlation to income, education, unemployment, crowded housing and years of residency at the group level. RESULTS: Crowded housing and low income at a group level were correlated with rates of both notified cases of COVID-19 (Pearson`s correlation coefficient 0.77 and 0.52) and related hospitalisations (0.72, 0.50). In addition, low educational level and unemployment were correlated with a high number of notified cases. CONCLUSIONS: Immigrant groups living in disadvantaged socioeconomic positions are important to target with preventive measures for COVID-19. This must include targeted interventions for low-income families living in overcrowded households.

The First GAEN-Based COVID-19 Contact Tracing App in Norway Identifies 80% of Close Contacts in "Real Life" Scenarios.

The coronavirus disease 2019 (COVID-19) response in most countries has relied on testing, isolation, contact tracing, and quarantine (TITQ), which is labor- and time-consuming. Therefore, several countries worldwide launched Bluetooth-based apps as supplementary tools. The aim of using contact tracing apps is to rapidly notify people about their possible exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thus make the process of TITQ more efficient, especially upon exposure in public places. We evaluated the Norwegian Google Apple exposure notification (GAEN)-based contact tracing app Smittestopp v2 under relevant "real-life" test scenarios. We used a total of 40 devices, representing six different brands, and compared two different exposure configurations, experimented with different time thresholds and weights of the Bluetooth attenuation levels (buckets), and calculated the true notification rates among close contacts (≤2 m and ≥15 min) and false notification of sporadic contacts. In addition, we assessed the impact of using different operating systems and locations of the phone (hand/pocket). The best configuration tested to trigger exposure notification resulted in the correct notification of 80% of the true close contacts and incorrect notification of 34% of the sporadic contacts. Among those who incorrectly received notifications, most (67%) were within 2 m but the duration of contact was <15 min and thus they were not, per se, considered as "close contacts." Lower sensitivity was observed when using the iOS operating systems or carrying the phone in the pocket instead of in the hand. The results of this study were used to improve and evaluate the performance of the Norwegian contact-tracing app Smittestopp.

Import and transmission of Mycobacterium orygis and Mycobacterium africanum, Norway.

BACKGROUND: The aim of the current study was to improve our understanding of the origins and transmission of Mycobacterium africanum (MAF) in Norway. METHODS: Whole-genome sequences (WGS) were generated for all (n = 29) available clinical isolates received at the Norwegian National Reference Laboratory for Mycobacteria (NRL) and identified as MAF in Norway, in the period 2010-2020. Phylogenetic analyses were performed. RESULTS: The analyses indicated several imports of MAF lineage 6 from both East and West African countries, whereas MAF lineage 5 was restricted to patients with West African connections. We also find evidence for transmission of MAF in Norway. Finally, our analyses revealed that a group of isolates from patients originating in South Asia, identified as MAF by means of a commercial line-probe assay, in fact belonged to Mycobacterium orygis. CONCLUSIONS: Most MAF cases in Norway are the result of import, but transmission is occurring within Norway.

COVID-19 among immigrants in Norway, notified infections, related hospitalizations and associated mortality: A register-based study.

Aim: Research concerning COVID-19 among immigrants is limited. We present epidemiological data for all notified cases of COVID-19 among the 17 largest immigrant groups in Norway, and related hospitalizations and mortality. Methods: We used data on all notified COVID-19 cases in Norway up to 18 October 2020, and associated hospitalizations and mortality, from the emergency preparedness register (including Norwegian Surveillance System for Communicable Diseases) set up by The Norwegian Institute of Public Health to handle the pandemic. We report numbers and rates per 100,000 people for notified COVID-19 cases, and related hospitalizations and mortality in the 17 largest immigrant groups in Norway, crude and with age adjustment. Results: The notification, hospitalization and mortality rates per 100,000 were 251, 21 and five, respectively, for non-immigrants; 567, 62 and four among immigrants; 408, 27 and two, respectively, for immigrants from Europe, North-America and Oceania; and 773, 106 and six, respectively for immigrants from Africa, Asia and South America. The notification rate was highest among immigrants from Somalia (2057), Pakistan (1868) and Iraq (1616). Differences between immigrants and non-immigrants increased when adjusting for age, especially for mortality. Immigrants had a high number of hospitalizations relative to notified cases compared to non-immigrants. Although the overall COVID-19 notification rate was higher in Oslo than outside of Oslo, the notification rate among immigrants compared to non-immigrants was not higher in Oslo than outside. Conclusions: We observed a higher COVID-19 notification rate in immigrants compared to non-immigrants and much higher hospitalization rate, with major differences between different immigrant groups. Somali-, Pakistani- and Iraqi-born immigrants had especially high rates.

Targeting TB or MRSA in Norwegian municipalities during 'the refugee crisis' of 2015: a framework for priority setting in screening.

IntroductionIn 2015, there was an increase in the number of asylum seekers arriving in Europe. Like in other countries, deciding screening priorities for tuberculosis (TB) and meticillin-resistant Staphylococcus aureus (MRSA) was a challenge. At least five of 428 municipalities chose to screen asylum seekers for MRSA before TB; the Norwegian Institute for Public Health advised against this.AimTo evaluate the MRSA/TB screening results from 2014 to 2016 and create a generalised framework for screening prioritisation in Norway through simulation modelling.MethodsThis is a register-based cohort study of asylum seekers using data from the Norwegian Surveillance System for Communicable Diseases from 2014 to 2016. We used survey data from municipalities that screened all asylum seekers for MRSA and denominator data from the Directorate of Immigration. A comparative risk assessment model was built to investigate the outcomes of prioritising between TB and MRSA in screening regimes.ResultsOf 46,090 asylum seekers, 137 (0.30%) were diagnosed with active TB (notification rate: 300/100,000 person-years). In the municipalities that screened all asylum seekers for MRSA, 13 of 1,768 (0.74%) were found to be infected with MRSA. The model estimated that screening for MRSA would prevent eight MRSA infections while prioritising TB screening would prevent 24 cases of active TB and one death.ConclusionOur findings support the decision to advise against screening for MRSA before TB among newly arrived asylum seekers. The model was an effective tool for comparing screening priorities and can be applied to other scenarios in other countries.

Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study.

BACKGROUND: Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016. METHODS: This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. We obtained data from MSIS and from a standardized form that was sent to health care providers at the time of patient notification to MSIS. We determined completion rates. Pearson's chi squared test was used to study associations between pairs of categorical variables and separate crude and multivariable logistic regression models were used to identify factors associated with treatment completion and adverse drug effects. RESULTS: We obtained information on treatment completion from 719 of the 726 individuals notified for LTBI treatment in 2016. Overall, 91% completed treatment. Treatment completion was highest in the foreign-born group [foreign-born, n = 562 (92%) vs Norwegian-born, n = 115 (85%), p = 0.007]. Treatment completion did not differ significantly between prescribed regimens (p = 0.124). Adverse events were the most common reason for incomplete treatment. We found no significant differences in adverse events when comparing weekly rifapentine (3RPH) with three months daily isoniazid and rifampicin (3RH). However, there were significantly fewer adverse events with 3RPH compared to other regimens (p = 0.037). Age over 35 years was significantly associated with adverse events irrespective of regimen (p = 0.024), whereas immunosuppression was not significantly associated with adverse events after adjusting for other variables (p = 0.306). Treatment under direct observation had a significant effect on treatment completion for foreign-born (multivariate Wald p-value = 0.017), but not for Norwegian-born (multivariate Wald p-value = 0.408) individuals. CONCLUSIONS: We report a very high treatment completion rate, especially among individuals from countries with high TB incidence. The follow-up from tuberculosis-coordinators and the frequent use of directly observed treatment probably contributes to this. Few severe adverse events were reported, even with increased age and in individuals that are more susceptible. While these results are promising, issues of cost-effectiveness and targeting treatment to individuals at highest risk of TB are important components of public health impact.

Genome-based transmission modelling separates imported tuberculosis from recent transmission within an immigrant population.

In many countries the incidence of tuberculosis (TB) is low and is largely shaped by immigrant populations from high-burden countries. This is the case in Norway, where more than 80 % of TB cases are found among immigrants from high-incidence countries. A variable latent period, low rates of evolution and structured social networks make separating import from within-border transmission a major conundrum to TB control efforts in many low-incidence countries. Clinical Mycobacterium tuberculosis isolates belonging to an unusually large genotype cluster associated with people born in the Horn of Africa have been identified in Norway over the last two decades. We modelled transmission based on whole-genome sequence data to estimate infection times for individual patients. By contrasting these estimates with time of arrival in Norway, we estimate on a case-by-case basis whether patients were likely to have been infected before or after arrival. Independent import was responsible for the majority of cases, but we estimate that about one-quarter of the patients had contracted TB in Norway. This study illuminates the transmission dynamics within an immigrant community. Our approach is broadly applicable to many settings where TB control programmes can benefit from understanding when and where patients acquired TB.

Tuberculosis Outbreak in an Educational Institution in Norway.

Within 1 week in April 2013, three cases of pulmonary tuberculosis (TB) were reported among students attending training sessions at an educational institution in Oslo, Norway. By the end of October 2013, a total of nine epidemiologically linked cases had been reported. The outbreak encompassed a total of 24 cases from 2009 to 2014, among which all of the 22 Mycobacterium tuberculosis isolates available had identical mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) profiles (MtbC15-9 code 10287-189) belonging to the Beijing lineage. Whole-genome sequencing (WGS) of the M. tuberculosis isolates revealed 20 variable nucleotide positions within the cluster, indicating a clonal outbreak. The most likely index case was identified and diagnosed in Norway in 2009 but was born in Asia. WGS analyses verified that all of the cases were indeed part of a single transmission chain. However, even when combining WGS and intensified contact tracing, we were unable to fully reconstruct the TB transmission events.

Immigrant screening for latent tuberculosis in Norway: a cost-effectiveness analysis.

The incidence of tuberculosis (TB) disease has increased in Norway since the mid-1990s. Immigrants are screened, and some are treated, for latent TB infection (LTBI) to prevent TB disease (reactivation). In this study, we estimated the costs of both treating and screening for LTBI and TB disease, which has not been done previously in Norway. We developed a model to indicate the cost-effectiveness of four different screening algorithms for LTBI using avoided TB disease cases as the health outcome. Further, we calculated the expected value of perfect information (EVPI), and indicated areas of LTBI screening that could be changed to improve cost-effectiveness. The costs of treating LTBI and TB disease were estimated to be €1938 and €15,489 per case, respectively. The model evaluates four algorithms, and suggests three cost-effective algorithms depending on the cost-effectiveness threshold. Screening all immigrants with interferon-gamma release assays (IGRA) requires the highest threshold (€28,400), followed by the algorithms "IGRA on immigrants with risk factors" and "no LTBI screening." EVPI is approximately €5 per screened immigrant. The costs for a cohort of 20,000 immigrants followed through 10 years range from €12.2 million for the algorithm "screening and treatment for TB disease but no LTBI screening," to €14 million for "screening all immigrants for both TB disease and LTBI with IGRA." The results suggest that the cost of TB disease screening and treatment is the largest contributor to total costs, while LTBI screening and treatment costs are relatively small. Increasing the proportion of IGRA-positive immigrants who are treated decreases the costs per avoided case substantially.

Tuberculosis outbreak in Eastern Norway.

BACKGROUND: Tuberculosis is a rare disease in Norway, especially among those who are born here. Contact tracing for cases of pulmonary tuberculosis is essential to find others who are ill or infected, and to prevent further infection. This article describes the investigation of an outbreak in which many of those infected or ill were Norwegian adolescents. MATERIAL AND METHOD: Nine persons directly or indirectly associated with the same educational institution were diagnosed with tuberculosis in 2013. Genetic testing of tuberculosis bacteria linked a further 13 cases of the disease reported in Eastern Norway during the period 2009-2013 to the outbreak. Information from the Norwegian Surveillance System for Communicable Diseases (MSIS) was used to investigate the outbreak, and information was also retrieved on exposure and contact networks. RESULTS: The first patient at the educational institution had long-term symptoms before diagnosis. Contact tracing for this case included 319 persons, of whom eight were ill, 49 infected and 37 received preventive therapy. The extent of contract tracing for the remaining 21 cases varied and included a total of 313 persons, of whom two were found to be ill (included in the 21 cases), 30 were infected and 12 received preventive therapy. INTERPRETATION: Delayed diagnosis led to an unusually large tuberculosis outbreak in a Norwegian context. The extent of contact tracing varied with no obvious relation to the infectiousness of the index patient. The outbreak demonstrates the importance of continued vigilance with regard to tuberculosis as a differential diagnosis, also among patients born in Norway.

[Use of coercion pursuant to the Communicable Diseases Act 1995-2013]. / Tvangstiltak etter smittevernloven 1995-2013.

BACKGROUND: The Communicable Diseases Act came into force in 1995. The Act authorises coercive examination and isolation of infected individuals. We wished to investigate how the provisions on coercion in this Act have been practised. MATERIAL AND METHOD: We reviewed all the cases that had been processed by the National Commission for Communicable Diseases from 1995 to the end of 2013. We contacted doctors in regional health enterprises to collect information on any emergency decisions having been made. We collected information from the tuberculosis register on treatment outcomes for tuberculosis, and investigated how many patients disappeared from treatment during 1995-2013. RESULTS: The communicable diseases commission had treated 15 cases involving a total of 12 individuals. Nine of these suffered from contagious pulmonary tuberculosis, one had primary tuberculosis, one was suspected of having tuberculosis and one was HIV positive. Three of the patients had multidrug-resistant tuberculosis. The commission made two decisions on coercive examination/brief isolation and nine on coercive isolation, as well as two decisions on extended isolation. No decisions were made regarding coercive treatment. Only four of the nine patients with contagious pulmonary tuberculosis completed the treatment sequence. One emergency decision has been made since 2006. INTERPRETATION: The provisions on coercion have been practised restrictively. Amendments to them should be considered, especially with regard to the opportunity to make emergency decisions on isolation of persons with a known diagnosis. There is a need for clearer regulations regarding extended isolation, and the time needed for processing of cases involving requests for a decision by the communicable diseases commission should be reduced.

Are QALYs based on time trade-off comparable?--A systematic review of TTO methodologies.

A wide range of methods is used to elicit quality-of-life weights of different health states to generate 'Quality-adjusted life years' (QALYs). The comparability between different types of health outcomes at a numerical level is the main advantage of using a 'common currency for health' such as the QALY. It has been warned that results of different methods and perspectives should not be directly compared in QALY league tables. But do we know that QALYs are comparable if they are based on the same method and perspective?The Time trade-off (TTO) consists in a hypothetical trade-off between living shorter and living healthier. We performed a literature review of the TTO methodology used to elicit quality-of-life weights for own, current health. Fifty-six journal articles, with quality-of-life weights assigned to 102 diagnostic groups were included. We found extensive differences in how the TTO question was asked. The time frame varied from 1 month to 30 years, and was not reported for one-fourth of the weights. The samples in which the quality-of-life weights were elicited were generally small with a median size of 53 respondents. Comprehensive inclusion criteria were given for half the diagnostic groups. Co-morbidity was described in less than one-tenth of the groups of respondents. For two-thirds of the quality-of-life weights, there was no discussion of the influence of other factors, such as age, sex, employment and children. The different methodological approaches did not influence the TTO weights in a predictable or clear pattern. Whether or not it is possible to standardise the TTO method and the sampling procedure, and whether or not the TTO will then give valid quality-of-life weights, remains an open question.This review of the TTO elicited on own behalf, shows that limiting cost-utility analysis to include only quality life weights from one method and one perspective is not enough to ensure that QALYs are comparable.

Can the value choices in DALYs influence global priority-setting?

The "disability adjusted life years" (DALYs) are increasingly used as a tool for decision-making and for describing the distribution of the Global Burden of Disease. The "DALY" combines information about mortality and morbidity, with several value choices such as disability weighting, age-weighting and discounting. These value choices imply that life years are assigned different value, depending on the age and the health state they are in. How robust is the distribution of DALYs to changes in these value choices, and are the choices transparent at the point of use? We calculated the burden attributed to "developmental disability due to malnutrition" and "major depression" with alternative value choices in a simple sensitivity analysis. In particular, we explored the relation between disability weight, health state description and incidence rate. The formulae and information needed was found in the World Health Organisation (WHO) publications using DALYs, and in a survey among international health workers. We found that alternative age-weights, disability weights and discount rate led to an inversion in the ranking of the burden of the two conditions. The DALY loss attributed to "developmental disability due to malnutrition" increased from 14 to 90%, while that of "major depression" sunk from 86 to 10%. The value choices currently used, tend at underestimating the disease burden attributed to young populations and to communicable diseases and this goes against the renewed efforts of the WHO of targeting diseases that are typical of poor populations. While the value choices may be changed, lack of transparency is a more profound problem. At the point of use, the number of DALYs attributed to a condition cannot be fully disaggregated. Hence, one cannot know which part of a DALY loss reflects the age group affected, the prevalence, the mortality rates, the disability weight assigned to it, or to how the condition has been defined. A more transparent and useful approach, we believe, would be to present the years lost due to a disease, and the years lived with a disease separately, without disability weights, age-weights and discounting. This would keep the best of the DALY approach and come closer to the aim of disentangling science from advocacy.

Roughly right or precisely wrong? Systematic review of quality-of-life weights elicited with the time trade-off method.

OBJECTIVE: Cost-utility analysis is gaining importance as a tool for setting priorities in health care. The approach requires quality-of-life weights on a scale from 0.00 (corresponding to death) to 1.00 (corresponding to perfect health). Different methods and perspectives of the evaluators tend to give different results. Time trade-off (TTO) is the most commonly used method to elicit quality-of-life weights for quality-adjusted life-years (QALYs). How reliable are the results of this method, when limited to one specific perspective, as input for cost-utility analysis? METHOD: Systematic literature review of empirical studies in which the TTO is elicited by the respondent on their own behalf. RESULTS: In 56 papers, quality-of-life weights for 102 diagnostic groups were given. Ranking of the diagnostic groups according to their quality-of-life weights had no apparent relation to severity. One specific diagnostic group was assigned quality-of-life weights ranging from 0.39 to 0.84. Altogether, 57% of respondents did not trade any life-time at all in exchange for health improvements. The distributions studied were skewed towards 1.00 and were bimodal without a central tendency. The correlation between the TTO and related methods was generally weak. Possible explanations for the poor empirical properties of the TTO are inappropriate use of the method, lack of representative samples, or that the TTO does not measure what it claims to measure. CONCLUSION: In the light of these findings, the TTO elicited from the patient perspective, as currently practised, should not be used as an input for QALYs or for comparisons of diagnostic groups.

Is cost-effectiveness analysis preferred to severity of disease as the main guiding principle in priority setting in resource poor settings? The case of Uganda.

INTRODUCTION: Several studies carried out to establish the relative preference of cost-effectiveness of interventions and severity of disease as criteria for priority setting in health have shown a strong preference for severity of disease. These preferences may differ in contexts of resource scarcity, as in developing countries, yet information is limited on such preferences in this context. OBJECTIVE: This study was carried out to identify the key players in priority setting in health and explore their relative preference regarding cost-effectiveness of interventions and severity of disease as criteria for setting priorities in Uganda. DESIGN: 610 self-administered questionnaires were sent to respondents at national, district, health sub-district and facility levels. Respondents included mainly health workers. We used three different simulations, assuming same patient characteristics and same treatment outcome but with varying either severity of disease or cost-effectiveness of treatment, to explore respondents' preferences regarding cost-effectiveness and severity. RESULTS: Actual main actors were identified to be health workers, development partners or donors and politicians. This was different from what respondents perceived as ideal. Above 90% of the respondents recognised the importance of both severity of disease and cost-effectiveness of intervention. In the three scenarios where they were made to choose between the two, a majority of the survey respondents assigned highest weight to treating the most severely ill patient with a less cost-effective intervention compared to the one with a more cost-effective intervention for a less severely ill patient. However, international development partners in in-depth interviews preferred the consideration of cost-effectiveness of intervention. CONCLUSIONS: In a survey among health workers and other actors in priority setting in Uganda, we found that donors are considered to have more say than the survey respondents found ideal. Survey respondents considered both severity of disease and cost-effectiveness important criteria for setting priorities, with severity of disease as the leading principle. This pattern of preferences is similar to findings in context with relatively more resources. In-depth interviews with international development partners, showed that this group put relatively more emphasis on cost-effectiveness of interventions compared to severity of disease. These discrepancies in attitudes between national health workers and representatives from the donors require more investigation. The different attitudes should be openly debated to ensure legitimate decisions.