[Screening for tuberculosis before TNFα treatment in routine rheumatic care in Iceland. Result from the nationwide ICEBIO registry].

INTRODUCTION: Treatment with TNFα inhibitors (TNFαi) greatly increases the risk of reactivation of tuberculosis in rheumatic patients. Therefore, it is recommended to screen patients for tuberculosis before initiating TNFαi treatment. Iceland has a low prevalence of tuberculosis and BCG vaccination is not routine praxis. The purpose of this study was to review the results from TB-screening in routine praxis and to analyze whether changes in the screening process are to be recommended. MATERIAL AND METHODS: All patients with RA, PsA and AS who were registered in ICEBIO (1999-2014) due to TNFαi treatment were included. Data collection consisted of age, sex, start date of TNFαi treatment and results from a tuberculin skin test (TST) and chest x-ray. The data were then crosschecked with the Berkill registry, a nationwide database for TB. RESULTS: 756 individuals (58% female, mean-age of 54 years) were included. TST was negative in 614 cases (81%), 41 positive (5.4%), 9 false positives (1.2%) and 92 were missing (12%). 119 patients were registered in Berkill whereof 72 had a history of positive TST and 55 had been vaccinated, while 14 patients had been diagnosed with tuberculo-sis (where of 7 had negative TST on screening). Three patients were diagnosed with tuberculosis after the TNFi treatment. CONCLUSION: These results illustrate the importance of tuberculosis screening before initiating TNFαi treatment. Improvement in registration of TST results is necessary and whether interferon gamma release assays (IGRA) should be added to the screening process remains to be discussed.

HLA class II sequence variants influence tuberculosis risk in populations of European ancestry.

Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10(-13)) and PTB (OR = 1.25, P = 5.8 × 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10(-12))--both located between HLA-DQA1 and HLA-DRB1--and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells.

[Multidrug resistant tuberculosis in Iceland--case series and review of the literature]. / Fjölónaemir berklar á Islandi--tilfellaröd og yfirlit.

BACKGROUND: Multidrug resistant tuberculosis (MDR-TB) is a growing health problem in the world. Treatment outcomes are poorer, duration longer and costs higher. We report three cases of MDR-TB diagnosed in Iceland in a six year period, 2003-8. CASE DESCRIPTIONS: The first case was a 23-year-old immigrant with a prior history of latent TB infection treated with isoniazid. He was admitted two years later with peritoneal MDR-TB. He was treated for 18 months and improved. The second case was a 23-year-old immigrant diagnosed with pulmonary MDR-TB after having dropped out of treatment in his country of origin. Clinical and microbiological response was achieved and two years of treatment were planned. The third case involved a 27-year-old asymptomatic woman diagnosed with MDR-TB on contact tracing, because of her brother's MDR-TB. 18 months of treatment were planned. CONCLUSIONS: Clustering of cases of MDR-TB in the last six years, accounting for almost 5% of all Icelandic TB cases in the period, suggests that an increase in incidence might be seen in Iceland in coming years. The infection poses a health risk to the patients and the general public as well as a financial burden on the health care system. Emphasis should be put on rapid diagnosis and correct treatment, together with appropriate immigration screening and contact tracing.

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.

Lessons from the past: familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918.

The pandemic influenza of 1918 (Spanish flu) killed 21-50 million people globally, including in Iceland, where the characteristics and spread of the epidemic were well documented. It has been postulated that genetic host factors may have contributed to this high mortality. We identified 455 individuals who died of the Spanish flu in Iceland during a 6-week period during the winter of 1918, representing >92% of all fatal domestic cases mentioned by historical accounts. The highest case fatality proportion was 2.8%, and peak excess mortality was 162/100,000/week. Fatality proportions were highest among infants, young adults, and the elderly. A genealogical database was used to study relatedness and relative risk (RR) of the fatal influenza victims and relatives of their unaffected mates. The significance of these RR computations was assessed by drawing samples randomly from the genealogical database matched for age, sex, and geographical distribution. Familial aggregation of fatalities was seen, with RRs for death ranging from 3.75 for first-degree relatives (P < 0.0001) to 1.82 (P = 0.005), 1.12 (P = 0.252), and 1.47 (P = 0.0001) for second- to fourth-degree relatives of fatal influenza victims, respectively. The RRs within the families of unaffected mates of fatal influenza victims were 2.95 (P < 0.0001), 1.27 (P = 0.267), 1.35 (P = 0.04), and 1.42 (P = 0.001), for first- to fourth-degree relatives, respectively. In conclusion, the risk of death from the Spanish flu was similar within families of patients who succumbed to the illness and within families of their mates who survived. Our data do not provide conclusive evidence for the role of genetic factors in susceptibility to the Spanish flu.

[Viral hepatitis B and C among immigrants in Iceland]. / Lifrarbólga af vökdum lifrarbólguveira B og C hjá innflytjendum á Islandi.

BACKGROUND: Viral hepatitis B and C are a major health problem worldwide. The prevalence of these diseases varies throughout the world. In Iceland, the incidence of hepatitis B and C has increased in recent years. At the same time, the number of immigrants from countries where viral hepatitis is endemic, has also increased. The aim of this study was to investigate the epidemiology of hepatitis B and C among immigrants in Iceland. MATERIAL AND METHODS: Immigrants from outside the European Economic Area (EEA) were screened for hepatitis B and C. Medical records for the years 2000-2002 were reviewed for country of origin, viral serology and liver transaminases. Information was gathered from the State Epidemiologist's central registry of notifiable diseases and from the Icelandic Directorate of Immigration on the number of residence permits issued. RESULTS: 70% of all immigrants from countries outside the EEA during the study period were included in the study. Blood samples were obtained from 2946 immigrants. 83 (2.8%) had hepatitis B and 24 (0.8%) had hepatitis C. Prevalence of hepatitis B was highest among immigrants from Africa,11/171 (6.4%; 95% CI: 3.3-11.2%) and hepatitis C among immigrants from Eastern Europe, 16/1502 (1.1%; 95% CI: 0.6-1.7%). 482 (16%) had serological markers of previous hepatitis B infection. Of all registered cases of hepatitis B, immigrants were 56% and of hepatitis C 10%. CONCLUSIONS: 1. Majority of those diagnosed with hepatitis B during the study period were immigrants. 2. Among immigrants, hepatitis B was more prevalent than hepatitis C. 3) The high prevalence of hepatitis B justifies screening for the disease in this population.