Anders Koch

Paleo-Eskimo mtDNA Genome Reveals Matrilineal Discontinuity in Greenland

The Paleo-Eskimo Saqqaq and Independence I cultures, documented from archaeological remains in Northern Canada and Greenland, represent the earliest human expansion into the New Worlds northern extremes. However, their origin and genetic relationship to later cultures are unknown. We sequenced a mitochondrial genome from a Paleo-Eskimo human by using 3400-to 4500-year-old frozen hair excavated from an early Greenlandic Saqqaq settlement. The sample is distinct from modern Native Americans and Neo-Eskimos, falling within haplogroup D2a1, a group previously observed among modern Aleuts and Siberian Sireniki Yuit. This result suggests that the earliest migrants into the New Worlds northern extremes derived from populations in the Bering Sea area and were not directly related to Native Americans or the later Neo-Eskimos that replaced them.

Intussusception in Early Childhood: A Cohort Study of 1.7 Million Children

Objective. To describe incidence and temporal trends of intussusceptions in Danish children during 1980 to 2001. Methods. A population-based cohort study was conducted of 1.67 million children who were younger than 5 years during 1980 to 2001 and were followed up for 6.66 million person-years. The Danish National Patient Registry was used to identify cases of intussusception in the cohort. Age-specific incidence rates were main outcome measure. Results. A total of 1814 cases of intussusception among children who were younger than 5 years were reported from 1980 to 2001. The incidence rate remained fairly constant during 1980 to 1990 but decreased by 55% (95% confidence interval: 43%–65%) from 1990 to 2001. The reduction was most pronounced among children aged 3 to 5 months. Conclusions. The incidence of intussusception among Danish children declined significantly during the 1990s, particularly among infants 3 to 5 months of age.

Frequency of atopy in the Arctic in 1987 and 1998.

Few studies have measured the frequency of atopy with objective measures, and most of these studies have been done in industrialised countries. We analysed serum samples from 859 15-80-year-old Greenlanders who had participated in population-based screening campaigns in 1987 and in 1998. We defined atopy as a positive result in an assay that tests for specific IgE against the eight most common inhalant allergens in one pool (grass, birch, mugwort, dog, cat, horse, Cladosporum herbarum, house dust mite). The frequency of atopy doubled between 1987 (39 [10%] of 392) and 1998 (87 [19%] of 467; risk ratio 1.88 [95% CI 1.31-2.68]). This increase was largest in 15-19-year olds, but also occurred in older people, suggesting that the risk factors responsible for the increase in atopy do not operate only in childhood.

Both high and low serum vitamin D concentrations are associated with tuberculosis: a case–control study in Greenland

Vitamin D deficiency has been associated with increased risk of tuberculosis (TB). Changes from a traditional to a Westernised diet among Greenlanders have resulted in reduced serum vitamin D, leading to considerations of whether preventive vitamin D supplementation should be introduced. The association between vitamin D status and TB was examined to assess the feasibility of vitamin D supplementation in Greenland. This was examined in a case-control study involving seventy-two matched pairs of TB patients (cases) and controls aged 8-74 years. Cases were diagnosed with TB during 2004-6 based on clinical findings in combination with either (1) positive Mycobacterium tuberculosis culture, (2) characteristic X-ray abnormalities together with a positive tuberculin skin test or a positive interferon-γ release assay or (3) characteristic histology. Controls were individually matched on age ( ± 5 years), sex and district. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured and OR of TB were the outcome. Compared with individuals with 25(OH)D concentrations between 75 and 140 nmol/l, individuals with concentrations < 75 nmol/l (OR 6.5; 95% CI 1.8, 23.5) or > 140 nmol/l (OR 6.5; 95% CI 1.9, 22.2) had higher risks of active TB (P = 0.003; adjustment for alcohol and ethnicity). Supplementing individuals with low vitamin D to normalise serum 25(OH)D concentrations was estimated to result in a 29% reduction in the number of TB cases. The study indicated that vitamin D supplementation may be beneficial to individuals with insufficient vitamin D concentrations but may increase the risk of TB among individuals with normal or high concentrations.

Mycoplasma genitalium presence, resistance and epidemiology in Greenland

Objectives . Greenland reports the highest rates of chlamydial infection and gonorrhea in the Arctic. Our objective was to determine the presence, and describe the basic epidemiology, of Mycoplasma genitalium for Greenland. Study design . Cross-sectional study. Methods . 314 residents from Nuuk and Sisimiut, between the ages of 15 and 65 years, participated in “Inuulluataarneq” (the Greenland Sexual Health Project) between July 2008 and November 2009. Participants provided self-collected samples for sexually transmitted infection (STI) testing and completed a sexual health survey. Descriptive statistics and logistic regression were used to summarize the basic characteristics of STI cases overall and M. genitalium and Chlamydia trachomatis specifically. Clinically relevant characteristics in each full model were gender (male or female), age (in years), age at sexual debut (in years), number of sexual partners in the past 3 months (continuous) and history of forced sex and community. Results . The overall prevalence of STIs was 19.0%, specifically: 9.8% for M. genitalium and 9.4% for C. trachomatis; 100% of M. genitalium-positive cases carried macrolide resistance determinants. Being female [OR = 3.2; 95% confidence interval (CI): 1.1–9.8] and younger age (OR = 0.9; 95% CI: 0.9–1.0) were associated with M. genitalium positivity. Age was also associated with C. trachomatis (OR = 0.9; 95% CI: 0.8–0.9) and STI positivity overall (OR = 0.9; 95% CI: 0.9–0.9). Conclusions . We observed a high prevalence of M. genitalium and macrolide resistance in this study. A better understanding of M. genitalium sequelae is needed to inform policy around testing, treatment, control and antibiotic use.

Cancer Susceptibility in Nasopharyngeal Carcinoma Families—A Population-Based Cohort Study

Undifferentiated nasopharyngeal carcinoma is a result of environmental factors, in particular EBV infection, affecting genetically susceptible individuals. The familial risk of nasopharyngeal carcinoma is among the highest of any malignancy. Whether this susceptibility is restricted to nasopharyngeal carcinoma is unknown as information on the risk of other cancers in relatives is limited. We did a population-based study of the cancer incidence in nasopharyngeal carcinoma families in Greenland, a nasopharyngeal carcinoma-endemic area. Using population-based registers, a cohort of all persons born in Greenland was followed from 1973 to 2002. In this cohort, 134 individuals developed nasopharyngeal carcinoma and their relatives were identified through registers and interviews. Subsequently, the occurrence of cancer was determined by linkage to the population-based cancer register and the risk of cancer in nasopharyngeal carcinoma relatives and nonrelatives compared by relative risks. Among 766 first-degree relatives, the relative risk of nasopharyngeal carcinoma following the family index case was 8.0 [95% confidence interval (95% CI), 4.1-14.0]. Sex and age of the relative or the index case had no modifying effect on the familial risk of nasopharyngeal carcinoma. The relative risks of carcinoma of the salivary glands, 8.4 (95% CI, 2.7-19.5), and uterine cervix, 2.2 (95% CI, 1.1-3.9), were also significantly increased. In families with multiple cases of nasopharyngeal carcinoma, the risk of other cancers than nasopharyngeal carcinoma was further increased. These results indicate that the increased risk of cancer in nasopharyngeal carcinoma families is not restricted to nasopharyngeal carcinoma, but extends to the virally associated cancers of the salivary glands and cervical uteri.

Comparison of Screening Procedures for Mycobacterium tuberculosis Infection Among Patients with Inflammatory Diseases

Objective. To test if Mycobacterium tuberculosis screening results differ among patients with inflammatory disease depending on whether the QuantiFeron TB-Gold test (QFT) or tuberculin skin test (TST) is used; and to evaluate if a possible difference is influenced by the presence of risk factors or immunosuppression. Methods. The interferon-γ response to in vitro stimulation of M. tuberculosis-specific antigens was measured with QFT and results were compared with TST. Associations to bacillus Calmette-Guerin (BCG) vaccination, risk factors, and immunosuppression were analyzed for both tests. Results. QFT and TST results were available for 294/302 and 241/302 patients, respectively; 234 had results from both tests. Twenty-one (7%) tested positive with QFT and 45 (19%) with TST. A positive QFT was associated with risk factors for M. tuberculosis infection: i.e., birth or upbringing in a TB-endemic area [risk ratio (RR) = 7.8, 95% CI 1.5–18.2, p < 0.001], previous TB treatment (RR 4.7, 95% CI 1.6–13.5, p = 0.005), and any latent TB infection risk factor (RR 4.7, 95% CI 2.1–11.0, p = 0.0002). Treatment with corticosteroids increased the risk for an inconclusive QFT result (RR 4.2, 95% CI 1.6–10.7, p = 0.04) and decreased the risk for a positive TST result (RR 0.4, 95% CI 0.1–1.0, p = 0.04). Agreement between the tests was low (kappa 0.2, 95% CI 0.02–0.3, p = 0.002). Conclusion. The study documented a high degree of discordant positive QFT and TST results. A positive QFT was more closely associated with risk factors for M. tuberculosis infection than the TST. The use of corticosteroids affected test outcome by increasing the risk for an inconclusive QFT result and decreasing the risk for a positive TST result.

Classification of Hepatitis B Virus Genotype B into 2 Major Types Based on Characterization of a Novel Subgenotype in Arctic Indigenous Populations

Hepatitis B virus genotype B (HBV/B) has been classified into 5 subgenotypes. Except for Bj/B1 in Japan, the subgenotypes (Ba/B2-B5) have undergone recombination with HBV/C in the core promoter/precore/core genomic region. Phylogenetic analyses of complete sequences show that the Arctic strains belong to a novel subgenotype (HBV/B6) without the recombination, analogous to what is seen with Bj/B1. Comparison of 50 HBV/B6 carriers from the Arctic versus 50 Bj and 50 Ba age- and sex-matched carriers from Asia revealed that clinical characteristics of HBV/B6 carriers were similar to those of Bj/B1 carriers in Japan. The results suggest that HBV/B may be classified into nonrecombinant (Bj/B1 and B6) and recombinant (Ba/B2-B5) types.

International circumpolar surveillance system for invasive pneumococcal disease, 1999-2005

Disease rates are high among indigenous persons in Arctic countries, and PCV7 has resulted in decreased rates in North American children.

Kawasaki syndrome in Denmark.

Objective: To describe the epidemiologic characteristics of Kawasaki syndrome (KS) and to estimate national KS incidence rates among children in Denmark. Methods: A retrospective population-based study using hospital discharge records with a KS diagnosis for children younger than 15 years selected from the Danish National Hospital Register for 1981–2004. Incidence rates were calculated using the number of KS patients and corresponding census data. Results: During 1981–2004, 360 children younger than 15 years were hospitalized with KS in Denmark, with 73% younger than 5 years. In this age group, the average annual incidence of KS gradually increased from 1981 to 1999 and thereafter stabilized at 4.5 to 5.0 per 100,000 person-years. The incidence was greater for boys than for girls (RR = 1.6, 95% CI = 1.2–2.0) and was highest among infants younger than 1 year (4.5), declining with increasing age (P = 0.03). However, the age-specific decline in incidence was only observed for boys, whereas the incidence for girls remained unchanged by age. The median length of hospital stay was 12 days, and the incidence peaked in the winter months. Conclusions: Major epidemiologic characteristics identified among Danish childhood KS are consistent with those described in previous studies, such as highest incidence among young children and winter-seasonality. The KS incidence rate among children younger than 5 years in Denmark increased steadily during the early study period (coinciding with global recognition of KS) and seems to have stabilized from 1998–1999 onwards. Although the incidence among Danish children was lower than that reported for several other European countries, differences in methodology challenge definite comparisons.