Karin Ladefoged

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.

Ongoing tuberculosis transmission to children in Greenland

Inuit in the Arctic are experiencing an increase in tuberculosis cases, reaching levels in Greenland comparable to high-incidence countries. This prompted us to study the level of tuberculosis transmission to Greenlandic children. Specifically, we estimated the current prevalence of Mycobacterium tuberculosis infection (MTI) and the underlying annual risk of MTI. 2,231 Greenlandic school children aged 5–17 yrs (∼25% of the Greenlandic population in the relevant age group) were tested for MTI using the tuberculin skin test and the QuantiFERON®-TB Gold in-tube test. Subjects with dual-positive results were considered infected and subjects with dual-negative results uninfected. The children with discordant test results were classified as probably having MTI and analysed separately. 8.1% of the children had dual-positive test results. The annual risk of MTI was estimated as 0.80% (95% CI 0.67–0.92%) giving a cumulative risk at the 18th birthday of 13.4%. The annual risk of MTI varied substantially by ethnicity (0.87% in Inuit children, 0.02% in non-Inuit children; p<0.001) and by location (0.13% on the west coast, 1.68% on the south coast; p<0.001). M. tuberculosis transmission occurs at a very high level in Inuit children with pronounced geographic differences emphasising the need for immediate public health interventions.

Demographic and clinical characteristics in relation to patient and health system delays in a tuberculosis low-incidence country

Abstract Background: Delays in the diagnosis and treatment of tuberculosis (TB) are commonly encountered. Methods: A study was undertaken among pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients in a Danish university hospital to describe demographic and clinical characteristics in relation to delay. Results: Of the 313 patients enrolled, 213 (68%) were diagnosed with PTB and 100 (32%) with EPTB only. Logistic regression analysis of EPTB showed an association with female sex and non-Danish ethnicity. Mean total delay from onset of symptoms until initiation of TB treatment was 123 (95% confidence interval (CI) 106–138) days. Mean patient delay was significantly longer than mean health system delay: 90 (95% CI 74–105) vs 33 (95% CI 23–44) days (p < 0.0001). Delay was independent of ethnicity and significantly shorter for PTB patients compared to EPTB patients. Fever was found to be strongly predictive of a short patient delay (<1 month), whereas weight loss was associated with a long patient delay (>3 months). In contrast, weight loss was associated with a short health system delay (<1 week). Elevated inflammatory markers were also associated with a short delay in the diagnosis of TB. Conclusions: This study confirmed a typical delay of months in duration in the diagnosis and treatment of TB in the low endemic country of Denmark. Increased TB awareness is needed, in particular in communities with immigrants originating from high-endemic areas.

Population-based Survey of Invasive Bacterial Diseases, Greenland, 1995–2004

Invasive bacterial disease occurs frequently among native populations in the Arctic. Although a variety of bacteria are involved in invasive bacterial disease in Greenland, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus, and other staphylococci are responsible for most cases (69%); incidence varies according to region and ethnicity.

Short Communication: High Prevalence of Drug-Resistant Human Immunodeficiency Virus Type 1 in Treatment-Naïve Patients in Greenland

A molecular epidemiologic study of HIV-1 in Greenland showed distinct transmission clusters correlated with demographic and behavioral data. Resistance mutations were found in a majority of the pol sequences. The objective of the present study was to estimate prevalence of drug resistance in Greenland and identify transmission chains by comparing resistance data with phylogeny and treatment history. Of 60 untreated patients, 15 (25%) had primary resistance mutations. The most prevalent mutations were T69D/N (15%), K70R (15%), and M184V (10%). Four possible transmission chains were identified based on phylogeny and mutation profiles. The clusters consisted of treated and untreated patients and showed the same mutation profiles in both resistance and nonresistance positions. Prevalence of transmitted drug resistance in Greenland (25%) is higher than in Denmark where only 3% transmission was observed. Suboptimal use of nucleoside reverse transcriptase inhibitor (NRTI) in Greenland was reflected in the high prevalence of NRTI-related resistance in the patients. A combination of phylogeny and genotypic resistance tests enabled us to study the number of transmissions and how the virus was transmitted. Resistance mutations detected in untreated patients were backed up by the treatment history of index patients in the possible transmission chains and indicated that these drug-resistant variants were in fact transmitted and had not emerged due to unregistered drug intake.

Hepatocellular Carcinoma and Other Liver Disease Among Greenlanders Chronically Infected with Hepatitis B Virus: A Population-Based Study

BACKGROUND In Greenland, the prevalence of hepatitis B surface antigen carriers, reflecting chronic hepatitis B virus (HBV) infection, is 5%-10%. However, the incidence of cirrhosis and hepatocellular carcinoma in this population has been reported to be low. We investigated this discrepancy in a large population-based cohort study. METHODS In total, 8879 Greenlanders (16% of the population) were recruited for population-based surveys performed from May 5 to July 7, 1987, and from November 1 to November 21, 1998, with follow-up until March 31, 2010. HBV status was based on serological testing, supplemented by data from all available HBV registries in Greenland to determine changes in HBV status over time. Information on morbidity and mortality was obtained from the Patient Discharge Registry, the Cancer Registry, and the Central Registration System. Sex, age, ethnicity, and period-adjusted incidence rate ratios (IRRs) were estimated using Poisson regression. World standardized rates were derived from these and World Health Organization data. RESULTS The 650 chronically HBV-infected persons had higher rates of hepatocellular carcinoma (adjusted IRR = 8.70; 95% CI = 2.06 to 36.7), liver disease (adjusted IRR = 5.73, 95% CI = 3.52 to 9.34), and all-cause mortality (adjusted IRR = 1.47; 95% CI = 1.21 to 1.79) than the 5160 HBV-negative persons. However, the world standardized incidence rates of hepatocellular carcinoma (38.5 cancers per 100 000 person-years) and cirrhosis (24 cases per 100 000 person-years) among chronically HBV-infected persons were low compared with results from population-based studies from countries with low, intermediate, and high rates of endemic HBV infection. CONCLUSION The relatively low incidence of hepatocellular carcinoma and other HBV-related morbidity among chronic HBV-infected persons in Greenland suggest a more benign course of HBV among the Greenlandic Inuit than in populations in other parts of the world.

Effectiveness of the Targeted Hepatitis B Vaccination Program in Greenland

OBJECTIVES To evaluate the effectiveness of the hepatitis B virus (HBV) vaccination program in Greenland, which targets children born to mothers who are positive for HBV surface antigen (HBsAg), we determined vaccination coverage, levels of postvaccination antibodies, and frequency of breakthrough infections in at-risk children. METHODS We conducted a population-based retrospective cohort study with data from nationwide registries. We identified all children born to HBsAg-positive mothers from 1992 to 2007 and collected data on their HBV vaccination status. In 2008 to 2010, we tested the children for HBV core antibody, HBsAg, and anti-HBsAg antibody (HBsAb). RESULTS Of 4050 pregnant women, 3.2% were HBsAg positive. Of 207 children born to these women, 20% received no vaccinations, and only 58% received at least 3 vaccinations. At follow-up, HBsAb levels in vaccinated children were much lower than expected, and 8 (6%) of 140 at-risk children had breakthrough infections, with 4 chronically infected (persistently HBsAg positive). CONCLUSIONS The prevention program targeting children at risk for HBV in Greenland is ineffective. HBV vaccination should be included in the universal childhood vaccination program, and postvaccination HBsAb levels should be monitored.

Low Effectiveness of Highly Active Antiretroviral Therapy and High Mortality in the Greenland HIV-infected Population

Greenland is a high-income country with free access to human immunodeficiency virus (HIV) care, including highly active antiretroviral therapy (HAART). We aimed to examine the HIV prevalence, age and gender distribution, and the effectiveness of HAART on CD4 positive cell count, viral load (VL), and mortality in the Greenland HIV-infected population. In this population-based cohort study we collected demographic, clinical and biochemical data on all HIV-infected patients followed in health clinics since 1995. For each case, we identified 100 age- and gender-matched population controls. The HIV cohort included 103 patients of whom 91% were Inuit; 81% were infected heterosexually. Only 40% of the patients had a VL <400 copies/ml at 48 weeks after starting HAART, and patients on HAART had a substantial excess relative mortality compared with the general population (mortality rate ratio [MRR]: 10.6; 95% confidence interval [CI]: 6.9–16.4). After the introduction of HAART, the mortality decreased (MRR: 2.5; 95% CI 0.9–6.8), but remained high with a mortality rate of 62 per 1000 person-years (py) (95% CI 29–129). Our findings underline the difficulties of implementing successful HIV treatment even with unlimited economic resources and free access to health care.

Endocarditis in Greenland with special reference to Endocarditis caused bt Streptococcus Phneumoniae

Abstract Objectives. The aim of this retrospective study was to determine the incidence and outcome ofinfectious endocarditis in Greenland with an emphasis on pneumococcal endocarditis. Study design. Retrospective, non-interventional study. Methods. Review of files and medical history of all patients with infectious endocarditis from thePatient Registry in Greenland in the 11-year period 1995–2005. Results. There were 25 cases of endocarditis, giving an incidence rate of 4.0/100,000 per year.Twenty-four percent of these cases were caused by Streptoccous pneumonia, which is significantlymore frequent than in studies on Caucasian populations, where pneumococcal infection was seenin 1–3% of endocarditis cases. The overall mortality rate was 12%. Pneumococcal endocarditis(PE) had the clinical characteristics of fulminant disease with frequent heart failure, complicationsand need for surgery. Among cases with PE, 67% needed acute valve replacement and themortality rate was 33%. Conclusions. The high incidence rate, clinical characteristics and grave prognosis of PE areconsistent with another study of an Inuit population in Alaska.

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. To access the supplementary material to this article please see Supplementary files under Article Tools online