Dysglycaemia among tuberculosis patients without known diabetes in a low-endemic setting.

With a high prevalence of dysglycaemia (29.1%) among tuberculosis patients without previously known diabetes, this study highlights the importance of comanagement of tuberculosis and diabetes, even in a low-endemic setting https://bit.ly/3Gj0gmN.

The prevalence of diabetes among tuberculosis patients in Denmark.

SETTING: It is estimated that 25% of the world's population are infected with Mycobacterium tuberculosis and that 463 million people are living with diabetes mellitus (DM), a number that is increasing. Patients with DM have three times the risk of developing tuberculosis (TB) and there is significant interaction between DM and TB, suggesting that DM affects not only risk of TB but also TB presentation, treatment response and outcome. OBJECTIVE: The aim was determining the prevalence of DM among TB patients in Denmark and to assess risk factors. DESIGN: Patient files from all notified TB cases in Denmark from 2009 to 2014 were retrospectively assessed. RESULTS: In total, 1912 patients were included and 5.0% had DM. Patients with DM were older, had more comorbidities, came from outside Denmark, and had a higher mortality compared to non-DM-patients. None of the patients from Greenland had DM. Patients with low socio-economic status had a low prevalence of DM. We found a higher prevalence of DM among Danish-born < 54 year and migrant ≥ 75 year compared to a Danish background population. CONCLUSION: We found a higher prevalence of DM among TB patients with known risk factors, and a surprisingly low prevalence among patients with low socioeconomic status and patients from Greenland.

Syphilis in Greenland, 2015 to 2019.

BACKGROUND: An increase in the incidence of syphilis was reported in Greenland from 2011 to 2014, and notification rates kept rising in the following years in spite of focused efforts. To better understand the syphilis epidemic, this study was conducted to describe the syphilis epidemic in Greenland from 2015 to 2019. METHODS: Syphilis cases and their characteristics were identified through reviews of electronic medical records and laboratory results in 3 different data sets: notifications to the National Board of Health, electronic prescriptions for benzathine penicillin, and the national laboratory database. Annual incidences were calculated stratified by sex, age, and region. RESULTS: The incidence of syphilis in Greenland increased from 107.4 to 246.8 cases per 100,000 inhabitants from 2015 to 2019. The incidence increased in both sexes and in nearly all regions, although with large regional differences. Especially the age group 15 to 29 years showed a substantial increase in incidence in 2018 and 2019. More females than males were infected (245 female cases vs. 178 male cases). CONCLUSIONS: The burden of syphilis in Greenland is high, primarily among the age group 15 to 29 years. A higher incidence among females than among males was found, suggesting mainly heterosexual transmission, as seen for other sexually transmitted infections in Greenland.

Prevalence of hepatitis B and C at a major tuberculosis centre in Denmark.

BACKGROUND: Denmark is a low-prevalence country for tuberculosis (TB), hepatitis B (HBV), and hepatitis C (HCV) but the three diseases have similar sociodemographic risk factors. We estimated the prevalence and possible risk factors of HBV and HCV among TB-patients in a large TB clinic in Denmark. METHODS: All patients starting anti-TB-treatment at Copenhagen University Hospital, Herlev-Gentofte from April 1st 2018 through June 1st 2019 were included. Results from HBV and HCV testing as well as sociodemographic information were collected. Risk factor analyses were carried out using descriptive statistics. RESULTS: Of 82 patients tested for HBV, one (1.2%) had chronic HBV and 16 (19.5%) had serocleared HBV. Of 91 patients tested for HCV, three (3.3%) had chronic HCV and one (1.1%) had serocleared HCV. Country of origin other than Denmark was significantly associated with HBV-seropositivity among TB-patients, particularly patients from Greenland, Asia, Africa and Eastern Europe. No other significantly associated risk factors were found. CONCLUSION: The prevalences of chronic and prior HBV and HCV among TB-patients were lower compared to studies in TB high endemic areas but higher than those found in the Danish background population. We calculated the number needed to test to find one patient with HBV ranged between 27 and 83 and we suggest continuing screening of chronic HBV and HCV in TB-patients in Denmark.

[Infectious diseases with public health impact in Greenland].

Infectious diseases cause significant morbidity in Greenland. In the first part of the 20th century, the incidence of tuberculosis (TB) in Greenland was extremely high. While focused efforts led to marked reduction in incidence, TB is still a challenge. Likewise, the prevalence of chronic otitis media is very high in Greenland with significant developmental and social consequences from hearing loss and chronic ear discharge. Finally, while focused efforts have been made against sexually transmitted infections, the incidence of such diseases is still very high. This paper reviews these infections in Greenland.

Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit.

N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined the NAT2 enzyme-activity by caffeine test. No additional genetic variants were identified in the coding sequence of NAT2, so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel. Studying the enzyme activity by the ratio of the two caffeine metabolites AFMU and 1X in 260 participants showed a high rate of slow phenotypes with intermediate or rapid genotype. These misclassifications were mainly observed in urine samples with pH<3, a deviation from the standard protocol due to the field work character of the study, where immediate pH adjustment to pH=3.5 was not possible. We excluded these samples. For the remaining 143 individuals with pH>3, we observed a moderate level of discrepancies (19 of the 116 individuals with intermediate or rapid genotype status having a slow phenotype). Further investigation showed that drinking coffee and not tea or cola was the most important factor for high levels of both metabolites. The concordance between phenotype and genotype status with regard to slow metabolism supported the recommendation of lower isoniazid doses in individuals with slow genotype status in order to avoid liver injury, a frequent side effect. The phenotypical variation observed for individuals with intermediate or rapid genotype status warrants further research before increased dosing of isoniazid can be recommended.

Erythema nodosum and the risk of tuberculosis in a high incidence setting.

OBJECTIVE: This study estimates the erythema nodosum (EN) incidence in a tuberculosis (TB) endemic setting and evaluates the likelihood of a subsequent TB diagnosis among individuals with Mycobacterium tuberculosis infection (MTI) with or without EN. DESIGN: We estimated EN incidence rates (IRs) in East Greenland in 2010-2011 and conducted a cohort study following all individuals who tested positive for MTI from 1 January 2010 until 31 December 2012. A personal identifier allowed individual follow-up in the mandatory TB register. MTI was defined by a positive interferon-gamma release assay. TB incidence rate ratios (IRRs) among participants with or without EN were estimated with the Cox proportional hazard model. RESULTS: We identified 38 EN cases corresponding to an IR of 500/100,000 inhabitants/year. All cases were among individuals with MTI. The EN IR was 11.79 (95% CI 5.73-24.27) times higher for BCG-unvaccinated compared with BCG-vaccinated individuals. The TB IRR was 25 (95% CI 11-60) within 1 month of EN compared to individuals without EN. CONCLUSION: This study documents a high EN incidence in a TB endemic region. EN occurred only in individuals with MTI, and predominantly among BCG-unvaccinated individuals. EN was significantly associated with a TB diagnosis within 1 month of diagnosis.

Determination of NAT2 acetylation status in the Greenlandic population.

N-acetyltransferase 2 (NAT2) is a well-studied phase II xenobiotic metabolizing enzyme relevant in drug metabolism and cancerogenesis. NAT2 activity is largely determined by genetic polymorphisms in the coding region of the corresponding gene. We investigated NAT2 acetylation status in 1556 individuals from Greenland based on four different single nucleotide polymorphism (SNP) panels and the tagging SNP rs1495741. There was good concordance between the NAT2 status inferred by the different SNP combinations. Overall, the fraction of slow acetylators was low with 17.5 % and varied depending on the degree of Inuit ancestry; in individuals with <50 % Inuit ancestry, we observed more than 25 % slow acetylators reflecting European ancestry. Greenland has a high incidence of tuberculosis, and individual dosing of isoniazid according to NAT2 status has been shown to improve treatment and reduce side effects. Our findings could be a first step in pharmacogenetics-based tuberculosis therapy in Greenland.

Rapid change in the ciprofloxacin resistance pattern among Neisseria gonorrhoeae strains in Nuuk, Greenland: time to reconsider preventive and treatment strategies.

OBJECTIVES: Sexually transmitted infections (STIs), including infections with Neisseria gonorrhoeae (GC), are highly incident in Greenland. Since January 2011, GC testing has been performed on urine with nucleic acid amplification tests (NAATs) by strand displacement amplification (Becton Dickinson ProbeTec). Monitoring of GC antibiotic susceptibility by culture was introduced in Nuuk in 2012. Until 2014, no cases of ciprofloxacin-resistant GC strains were reported. In this paper, we report the finding of ciprofloxacin-resistant GC and describe the most recent incidence of GC infections in Greenland. METHODS: The number of urine NAATs and culture-positive swabs from January to October 2014 were obtained from the Central Laboratory at Queens Ingrid's Hospital in Nuuk and stratified on gender, place and period of testing. Incidence rates were estimated as number of urine NAAT * (12/10) per 100,000 inhabitants. Men in Nuuk with a positive NAAT for GC were encouraged to provide a urethral swab for culture and susceptibility testing. RESULTS: From January to October 2014, a total of 5,436 urine GC NAATs were performed on patients from Nuuk and 9,031 from the rest of Greenland. Of these, 422 (8%) and 820 (9%) were positive, respectively. From January to August, 6 (15%) cultures from Nuuk were ciprofloxacin resistant while in September and October, 26 (59%) were ciprofloxacin resistant (p<0.01). In total, 35 (40%) of 88 culture-positive isolates showed ciprofloxacin resistance. GC incidence in Nuuk was 3,017 per 100,000 inhabitants per year, compared to 2,491 per 100,000 inhabitants per year in the rest of Greenland. CONCLUSION: Within a short period, a rapid and dramatic change in ciprofloxacin susceptibility among GC strains isolated in Nuuk was documented and recommendation for first line treatments has changed. Continued monitoring and rethinking of primary and secondary preventive initiatives is highly recommended in this high GC incidence setting.

The origin and emergence of an HIV-1 epidemic: from introduction to endemicity.

OBJECTIVES: To describe, at patient-level detail, the determining events and factors involved in the development of a country's HIV-1 epidemic. DESIGN: Clinical information for all recorded Greenlandic HIV-1 patients was analysed and correlated with both novel and previously analysed pol sequences, representing more than half of the entire Greenlandic HIV-1 epidemic. Archival blood samples were sequenced to link early infection chain descriptions to the subsequent epidemic. METHODS: In-depth phylogenetic analyses were used in synergy with clinical information to assess number of introductions of HIV-1 into Greenland, the source of geographic origin, time of epidemic introduction and its epidemiological characteristics such as initial transmission chain, geographic dispersal within Greenland, method of infection, cluster size, sociological and behavioural factors. RESULTS: Despite its small population size and isolated geographic location, data support at least 25 introductions of HIV-1 into Greenland. Only a single of these led to an epidemic. This introduction occurred between 1985 and 1986, and the epidemic cluster is still active. Facilitating factors for the emergence and spread of the epidemic cluster include a rapid transition from MSM to heterosexual spread, high prevalence of other sexually transmitted diseases, rapid dispersal to larger cities and early emergence in a distinct subpopulation with high-risk behaviour including disregard for condomizing. CONCLUSIONS: The synergistic use of disparate data categories yields such unique detail, that the Greenland epidemic now serves as a model example for the epidemic emergence of HIV-1 in a society. This renders it suitable for testing of present and future sequence-based epidemiological methodologies.

High prevalence of atrial fibrillation among Greenlanders with ischemic stroke - atrial fibrillation found in more than 30% of cases.

OBJECTIVES: To estimate the prevalence of atrial fibrillation among Greenlanders with ischemic stroke. STUDY DESIGN: A cross-sectional study. METHODS: Information on atrial fibrillation and vitamin K antagonistic treatment at admittance and at discharge was obtained for Greenlanders admitted to Queen Ingrid's Hospital in Nuuk with an ischemic stroke in 2011 or in 2012 with methods described in details elsewhere. RESULTS: Of 139 patients (64 males and 75 females) Greenlanders with an ischemic stroke in 2011 (n=74) or 2012 (n=65), 5.0% (n=7) had known atrial fibrillation prior to stroke compared to 32.4% (n=45) after discharge (p<0.01). CONCLUSIONS: More than 30% of ischemic stroke patients in this study had atrial fibrillation and only 5% were diagnosed prior to the stroke, suggesting that unknown atrial fibrillation is a substantial risk factor of ischemic stroke among Greenlanders.

Incidence of Greenlandic stroke-survivors in Greenland: a 2-year cross-sectional study.

OBJECTIVES: To estimate age- and gender-specific incidence rates among Greenlandic stroke-survivors. STUDY DESIGN: The study was performed as a cross-sectional observational study. METHODS: All Greenlandic patients admitted to Queen Ingrid's Hospital (QIH) with stroke in 2011 and 2012 were included in the study. Data were obtained from patient files and the Central Civil Registration System. Age- and gender-specific incidence rates were estimated as cases/100,000 adults/year. Direct age-standardized incidence rate was calculated using the WHO 2000-2005 population as the standard. RESULTS: In 2011 and 2012, 156 cases of stroke were registered, 72 (46.2%) males and 84 (53.8%) females. The overall incidence rate of stroke was 155/100,000 person-years (95% CI 121-190), with ischemic stroke accounting for 89.1% of these. No significant differences were seen between men and women. Direct age-standardized incidence rate was 149/year/100,000 (95% CI 192-264). Median age at time of diagnosis was 60 years (interquartile range 53-69). CONCLUSIONS: This study reports an age-standardized all-stroke incidence rate of Greenlandic stroke-survivors in Greenland within the wide range as incidences in Western Europe. A noticeable difference when compared to Denmark was that male and female incidence were approximately the same, and that incidence rates were high in the younger age groups. The majority of strokes were of ischemic origin.

The HIV epidemic in Greenland--a slow spreading infection among adult heterosexual Greenlanders.

INTRODUCTION: We aimed to characterise the HIV epidemic in Greenland and to determine incidence, prevalence, mortality rates (MR) and specific causes of deaths. STUDY DESIGN: The study design used was population-based nationwide cohort study. METHODS: We included all patients diagnosed with HIV in Greenland before 2011. Data were obtained from patient files, death certificates and the mandatory reports of HIV cases. Incidence and prevalence were estimated as cases/100,000 adults/year and MR as deaths/1,000 person-years (PYR). MRs were estimated for the pre-HAART (≤1996), early-HAART (1997-2004) and late-HAART (≥2005) periods. Deaths were considered AIDS related, if CD4 count <6 months before death was <200 cells/µL and/or an AIDS-related event occurred <12 months of death. RESULTS: We identified 171 cases of HIV among adult Greenlanders. Of these, 133 (78%) were infected in Greenland, 17 (10%) in Denmark and 21 (12%) in other places. The majority was infected through heterosexual contact [127 (74%)], 30 (18%) through homosexual contact, 3 (2%) through intravenous drug use and 11 (6%) through other or unknown routes of transmission. The median age at HIV diagnosis was 46 years (interquartile range 34-56). The incidence increased from 3.8 before 1989 to 29.7 cases/100,000 adults/year in the late 1990s. The incidence has slowly declined to approximately eight cases/100,000 adults/year. Prevalence increased to a maximum in 2009 (174.9/100,000 inhabitants), and slowly declined since then. A total of 79 have died and 25 have emigrated. MRs were high in the pre- and early-HAART periods, 65.3 [95% confidence intervals (CI) 40.0-106.6] and 87.0 [95% CI 63.5-119.0], and a large fraction of deaths were AIDS related. In the late-HAART period, MR has declined markedly to 53.4 (95% CI 35.8-79.7) with a substantial decline in AIDS-related MR. CONCLUSION: Heterosexual contact is the main route of HIV infection and the patients are diagnosed at a median age of 46. The incidence of newly diagnosed HIV patients has decreased markedly since year 2000. Mortality is high although declining in recent years.