Risk factors for Mycobacterium tuberculosis infection among children in Greenland

Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152 Research 741 Risk factors for Mycobacterium tuberculosis infection among children in Greenland Bolette Søborg,a Aase Bengaard Andersen,b Mads Melbye,a Jan Wohlfahrt,a Mikael Andersson,a Robert J Biggar,a Karin Ladefoged,c Vibeke Ostergaard Thomsend & Anders Kocha Introduction Although Greenland has experienced steady improvement in general living standards since World War II, tuberculosis (TB) remains a major health problem throughout the country.1,2 Overall TB incidence in Greenland doubled in the 1990s3 and still remained at 130 cases per 100 000 in 2010.1 The propor- tion of TB cases comprised of children under the age of 15 years rose from 8% in 1990 to 25% in 1997.3 Because of this resurgence of TB, in 1999 national health authorities launched a TB control programme consisting of the vaccination of all neonates with bacille Calmette–Guérin (BCG), early case detection and the monitoring of treatment outcomes.4 In 2007 the programme was revised to include routine screening of children for Mycobacterium tuberculosis infection (MTI) at the ages of 6 and 16 years. Despite this effort, TB incidence and the risk of MTI among children remain high.4,5 Surprisingly, the resurgence of TB in Greenland is not linked to human immunodeficiency virus (HIV) infection or to multidrug resistant TB, both of which are still very uncommon in the country. As of 2010, only 157 HIV-positive cases had been registered despite free HIV testing and only one case of multi- drug resistant TB had been documented.1,6 Instead, it appears to result from microepidemic outbreaks in small towns and remote settlements. TB is 20 times more common among the Inuits of Arctic Canada and Alaska than among non-native white populations.7–11 This elevated risk suggests that even in resource–rich countries, TB control is difficult in small, hard- to-reach communities with limited health resources. In 2009, a World Health Organization group proposed a revision of current TB control, targeting strategies to minimize exposure to TB as measured by the presence of MTI.12 The revision raises the need to better understand the risk factors associated with MTI, especially at the local and regional level, since risk factor profiles vary from place to place and one programme will not necessarily be effective everywhere. The objective of this study was to explore the risk factors for MTI among Greenlandic children to help identify the children at highest risk of infection. Methods Study sites and population An ice cap covers 82% of Greenland’s territory, permitting settlements only in coastal areas. The population, which numbers 57 000, is 90% Inuit. Greenland is an integral part Abstracts in بيرع, 中文, Français, Pусский and Español at the end of each article. Objective To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection. Methods Between 2005 and 2007, 1797 Greenlandic schoolchildren in five different areas were tested for MTI with an interferon gamma release assay (IGRA) and a tuberculin skin test (TST). Parents or guardians were surveyed using a standardized self-administered questionnaire to obtain data on crowding in the household, parents’ educational level and the child’s health status. Demographic data for each child – i.e. parents’ place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother’s age when the child was born – were also extracted from a public registry. Logistic regression was used to check for associations between these variables and MTI, and all results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Children were considered to have MTI if they tested positive on both the IGRA assay and the TST. Findings The overall prevalence of MTI was 8.5% (152/1797). MTI was diagnosed in 26.7% of the children with a known TB contact, as opposed to 6.4% of the children without such contact. Overall, the MTI rate was higher among Inuit children (OR: 4.22; 95% CI: 1.55–11.5) and among children born less than one year after the birth of the next older sibling (OR: 2.48; 95% CI: 1.33–4.63). Self-reported TB contact modified the profile to include household crowding and low mother’s education. Children who had an older MTI-positive sibling were much more likely to test positive for MTI themselves (OR: 14.2; 95% CI: 5.75–35.0) than children without an infected older sibling. Conclusion Ethnicity, sibling relations, number of household residents and maternal level of education are factors associated with the risk of TB infection among children in Greenland. The strong household clustering of MTI suggests that family sources of exposure are important. a Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. b Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. c Department of Internal Medicine, Queen Ingrid’s Hospital, Nuuk, Greenland. d International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark. Correspondence to Bolette Søborg (e-mail: bot@ssi.dk). (Submitted: 26 November 2010 – Revised version received: 8 July 2011 – Accepted: 10 July 2011 – Published online: 24 August 2011 ) Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152742 Bolette Søborg et al.Mycobacterium tuberculosis infection in Greenlandic children Research of the Kingdom of Denmark but is self- governing. Although its population is less affluent than that of Denmark, it is nonetheless wealthy by developing country standards, with a gross national product per capita of 20 000 United States dollars. Health care is provided by the government at Danish standards.13 The capital, Nuuk, has one national hos- pital; a local hospital exists in each of the country’s five administrative districts, along with additional health centres and nursing stations or clinics. Care is free of charge. However, inequities have not been fully eradicated mainly because small and isolated communities have limited health-care resources and the least experienced health-care workers.14 Physicians, typically from Denmark, have difficulty communicating with the Inuit population and are usually on short-term assignments, so that gaps be- tween postings sometimes occur. Living in a small community is an independent risk factor for TB disease.15 The current study, cross-sectional in design, included all schoolchildren in five different towns and nearby settlements across Greenland: Tasiilaq (November, 2005) in eastern Green- land; Narsaq (May, 2006), Qaqortoq (August, 2006) and Nanortalik (Sep- tember 2006) in southern Greenland; and Sisimiut (May, 2007), in western Greenland. School attendance is man- datory everywhere in the country for children aged from 6 to 16 years. On 31 December 2006, the study area had 2880 eligible children in that age group (i.e., 25% of the entire Greenlandic pop- ulation of children 6 to 16 years old), all of whom were invited to participate in the study. We included all schools and identified the children through school protocols. The sur ve ys were c onducte d through all local schools in the desig- nated survey areas. Prior to the surveys, the school sent every student home with information about the study and a questionnaire in both Danish and Greenlandic. Enrolment required in- formed consent signed by a parent or guardian. During the survey a nurse or doctor measured every child’s height and weight using a scale and a measur- ing tape. These measures were used to derive a body mass index (BMI) with a BMI percentile calculator specific for children. The calculation used the basic BMI formula: body weight in kilograms divided by the square of the height in metres. Results compare BMI-for-age percentiles with BMI-for-age growth charts.16 In Greenland, neonates have been vaccinated with BCG since 1949 except during the period from 1991 to 1996. We ascertained the BCG status of participating children retrospectively by inspecting detailed vaccination records maintained by community nurses at local health-care facilities. We drew a venous blood sample from each child and administered a tuberculin skin test (TST) to each of them. Risk factors We extracted demographic information on each child from the civil registra- tion system (CRS), which contains information on all Greenlanders.17 This included parents’ place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother’s age when the child was born. Children whose parents were both born in Greenland were con- sidered Inuit, as this method has been shown to accurately identify children of Inuit heritage.18 By having parents or caretakers complete a standardized self-administered questionnaire, we also obtained information on crowd- ing in the household (total number of dwellers, number of adults and number of children), parents’ educational level, health status of the study child and type of heating in the household. Mycobacterium tuberculosis infection The venous blood sample was used to test for MTI using the Quantiferon TB-Gold In-Tube (QFN) (Cellestis, Carnegie, Australia) interferon gamma release assay. The QFN was performed according to the manufacturer’s instruc- tions. All tests were corrected for back- ground reactivity. Interferon-γ (IFN-γ) results from white blood cell stimulation by the TB antigens were provided by the kit manufacturer (ESAT6, CFP-10 and TB 7.7). A test was considered positive and indicative of MTI if IFN-γ produc- tion was ≥ 0.35 international units per millilitre (IU/ml). The TST was applied to the dorsal aspect of the forearm by the intradermal Mantoux method using 2 tuberculin units (0.1 ml) of RT-23 purified pro- tein derivative (PPD) (Statens Serum Institut, Copenhagen, Denmark), and the result was read 72 hours later by an experienced examiner. According to current Greenlandic TB guidelines, an induration ≥ 12 mm in diameter at the injection site indicates a positive response. Some TST results were miss- ing because testing was refused or the child was lost to follow-up before the reading of the TST. A child was considered to have MTI only if he/she tested positive both on the QFN and on the TST, regardless of clinical status. Children with negative results on both tests were classified as uninfected. We treated all children with discor- dant test results as in need of evaluation for MTI and referred them for the same clinical evaluation and possible TB prophylaxis as children who were dually positive. Ethical considerations The study was approved by the Com- mission for Scientific Research in Greenland (approval No. 505–105). All participants with positive results on either the QFN or the TST were referred to the local medical centre for further evaluation, including a chest X- ray and clinical examination. Children diagnosed with clinically active TB were offered standard TB treatment; those with MTI were treated prophylactically with isoniazid. Statistical analysis We used logistic regression with the Proc Genmod procedure (SAS, Cary, USA) to calculate odds ratios (ORs) for the association between MTI and potential risk factors. We accounted for clustering of MTI within families by using generalized estimation equations. Initially, ORs were adjusted for age and sex only. Variables found to be statisti- cally significant were then entered into fully-adjusted models, which included ethnicity, maternal age, age gap between child and next older sibling, and region of residence. All adjustment variables are presented in the tables. Since contact with a known TB case has been reported to be a main predictor for MTI,19 we further explored whether such contact modified the risk factor pattern. We determined whether a risk factor was modified by contact with a Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152 743 Bolette Søborg et al. Mycobacterium tuberculosis infection in Greenlandic children Research TB case by assessing for interactions between the risk factor and TB contact after adjustment for each adjustment variable. We estimated age trends using the median age within each age group as a continuous variable. We examined the association between MTI and having an older sibling found to be infected dur- ing the survey for all children who had at least one older sibling in the study. Results The census recorded 2880 children of eligible age as residents of the study areas. However, migration of house- holds is common in Greenland and the exact number in residence is uncertain. Initially 2218 children (77% of the es- timated 2880 children) returned signed consent forms. Of these children, 1886 (85%) were successfully tested with both the QFN and TST. Eighty nine subjects had discordant QFN and TST results: 46 had a positive TST and a negative QFN; 25 had a positive QFN and a negative TST, and 18 had an inconclusive QFN and a negative TST. These subjects were not included in the main analyses. Thus, 1797 (81% of 2880 estimated children) had a defini- tive MTI assessment. The demographic characteristics of participating children and of children across Greenland in the same age groups are shown in Table 1. Age, gender, mother’s age when she gave birth to the child, mother’s total number of children and ethnicity were similar in the study population as in the total population of children in Greenland. In total, 152 (8.5%) of the 1797 children included in the analysis were positive for MTI. This included 48 (26.7%) of the 180 children with a known TB contact (10% of the whole) and 104 (6.4%) of the 1617 children without a known TB contact. Of the 180 children with a reported TB con- tact, 31% reported a household contact, 22% reported a school contact and 47% did not specify the type of contact. Of 180 children with TB contacts, 122 (68%) reported the time elapsed since the contact. In 52 such cases the contact was reported as having occurred within the past year. Positivity on both tests did not correlate with the time elapsed since the first known TB contact. Of the chil- dren who had a known TB contact but whose older siblings were uninfected, 13.9% were MTI positive, as opposed to 35.7% of the children who had at least one infected older sibling (sex- and age- adjusted OR:3.48; 95% CI: 0.80–15.1). An age gap of less than one year between the child and the closest older sibling was a risk factor (OR: 2.48; 95% CI: 1.33–4.63). Among children without a known TB contact, 2.9% were posi- tive for MTI when no older sibling was infected, whereas 27.3% were positive when at least one older sibling was in- fected (sex- and age-adjusted OR: 14.2; 95% CI: 5.75–35.0). During clinical follow-up of children dually positive, four were diagnosed as having clinically active TB as defined by positive X-ray findings or microbiological evidence of MTI. Table 2 (available at: http://www.who. int/bulletin/volumes/89/10/10-084152) presents age- and sex-adjusted and fully adjusted OR with 95% CIs. After adjustments for age and sex only, the following variables were significant risk factors: increasing age, Inuit ethnicity, young maternal age, narrow age gap (< 1 year) to next older sibling and region of residence (southern, highest; eastern, intermediate; western, lowest). After multivariate adjustment (full adjustment) the following variables were significantly associated with MTI: increasing age, Inuit ethnicity, narrow age gap to next older sibling and region of residence. Variables that were not associated with the risk of infection included: crowding as measured by the total number of dwellers or the number of children in the household, birth order, age difference in years between the child and the next younger sibling, co-morbidity in the child, father’s education level and type of heating facilities. Table 3 (available at: http://www.who. int/bulletin/volumes/89/10/10-084152) Table 1. Comparison of demographic characteristics of schoolchildren in study population (n = 1797) and Greenlandic schoolchildren in general Characteristic Study populationa Greenlandic school- childrenb Total (No.) 1797 10 593 Gender, No. (%) Male 892 (49.6) 5382 (50.8) Female 905 (50.4) 5211 (49.2) Age (years) Mean 11.0 11.2 SD 3.0 3.1 Median 11 12 Range 5–19 6–16 Ethnicity, No. (%)c Inuit 1734 (96.5) 10 126 (95.6) Non-Inuit 63 (3.5) 467 (4.4) Danish 53 (3.0) 417 (3.9) Other 10 (0.5) 50 (0.5) Mother’s age (years) at child’s birth Mean 26.7 26.4 SD 5.9 5.9 Median 27 26 Range 15–46 14–52 Mother’s total no. of liveborns (including study child) Mean 3.1 3.0 SD 1.6 1.5 Median 3 3 Range 1–11 1–11 SD, standard deviation. a Includes participating schoolchildren recruited from five survey districts across Greenland. b Includes all schoolchildren 6–16 years of age living in Greenland as of 31 December 2006 (data from the Danish Civil Registration System [CRS]). c Unlike the rest of the paper, this table presents ethnicity among the study population based on a child’s birthplace to facilitate the comparison with the total population of Greenland (data from the CRS). Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152744 Bolette Søborg et al.Mycobacterium tuberculosis infection in Greenlandic children Research shows the association between having MTI and each of the potential risk factors encountered in children with and without a reported TB contact. We checked whether the effect of each variable was modified by the presence or absence of a known TB contact. The variables whose effect was significantly modified by the presence of a known TB contact were domestic crowding (increased risk: P = 0.009) and mother’s education (decreased risk: P = 0.05). Region of residence was only associated with MTI among children without a known TB contact (P = 0.03), with children in southern Greenland having the highest risk. Discussion This study is, to our knowledge, the first one to have examined the rates of MTI and its risk factors in children living in the Arctic region. We found that contact with a patient with clinically active TB, increasing age, Inuit ethnicity, and a nar- row age difference between the child and the next older sibling were significantly associated with positivity for MTI. However, stratifying for contact with a known TB case modified this picture somewhat. Among the children in the study who had a known TB contact (10%), domestic crowding and low ma- ternal educational level were significant risk factors for MTI, while the only significant risk factor for MTI among children without a known TB contact was the region of residence. Thus, two different risk factor pat- terns for MTI exist among children in Greenland, with the presence or absence of a known TB contact being the de- finitive factor. Among children with a known TB contact, the increased risk of MTI associated with living in crowded conditions may be the result of both easier transmission of M. tuberculosis because of closer contact between family members or because more family mem- bers are infected with M. tuberculosis. Similarly, low maternal education, inso- far as it is linked to low socioeconomic status, may favour transmission of MTI within the household because of subop- timal hygienic standards and care for cases with TB. Other studies have also found low socioeconomic status to be associated with poorer general health, which may increase susceptibility to MTI among children living in house- holds with fewer resources.20 Even in children without a known TB contact, the source of infection appears to be within the household. A child’s risk of MTI was 14 times higher when an older sibling was found to be infected, even when the source of the infection was not known to be within the family. When two children within a family have MTI, both may have been exposed to a third active TB case or one child may have been sequentially exposed to the other. The finding that geographical region of residence was a risk factor for MTI in children without a known TB contact underlines the greater likelihood of community expo- sure when prevalence is high in the area. While this increased risk would also be true among children with known TB contact, M. tuberculosis exposure within the family dominated MTI risk, adjust- ing away the community-associated risk In children with and without TB contacts, the increasing risk of MTI with increasing age points to a cumula- tive risk of acquiring MTI over time, a finding also observed in other stud- ies.21,22 We have previously reported that the annual risk of MTI in Greenland is 0.8% per year, which translates into a prevalence of MTI of about 13% by the age of 18 years.5 Inuit ethnicity was also associated with a higher risk of MTI in children with or without a known TB contact. Both genetic and environmental fac- tors may be at play. Overall, little is known about the genetic susceptibil- ity to tuberculosis, but some have reported that polymorphisms in the genes for mannose binding lectin and for the interferon gamma receptor are associated with susceptibility to M. tuberculosis.23–25 In Greenland, social determinants probably increase the risk of MTI among Inuit children, since Inuit families tend to be larger, to live in more crowded conditions and to be less educated than families in which at least one parent is Danish.26 A narrow age gap between a child and a next-older-sibling with MTI was a risk factor for TB both among children with a known TB contact and those without. This finding has been docu- mented in studies of other infectious agents27,28 but not, to our knowledge, in studies on MTI. Traditionally, children with active TB disease are not consid- ered infectious because they excrete few bacteria. However, in adolescence TB begins to resemble the adult form of the disease and can become sputum posi- tive, as in adults, which poses the risk of transmission.29–31 It is also possible that a narrow age gap between siblings acts as a proxy for closer interaction with elder siblings or a common social circle, both of which could make for a shared source of infection. In 2007, the Greenlandic Director- ate of Health revised the national TB programme by adding public informa- tion campaigns and educational materi- als for disease prevention programmes.32 Our findings, based on MTI as the outcome, suggest that future campaigns should primarily target the Inuit popula- tion living in high-incidence regions and the inhabitants of small communities and settlements, and that efforts should be made to enhance contact tracing within families of low socioeconomic status. In Greenland, TB screening is routinely performed when children enter school and again when they gradu- ate. This study has shown that if a child screens positive for MTI, intensive in- vestigation of all members of the family should be undertaken promptly. Our study has several strengths. The study population comprised approxi- mately 17% of the total population of Greenland in the relevant age groups. The sample population was almost identical in its demographic character- istics to the population of Greenland as a whole. Because enrolment in the study was based on school attendance, which is mandatory in Greenland, our study sample is not likely to be biased by differences in access to health care. We know from previous experience that school lists, which form the basis for registering children in the communities, often include children temporarily or permanently absent from the area. We therefore consider a participation rate of 62% to be acceptable and the sampled population to be representative of the entire population of Greenland. Fur- thermore, we diagnosed MTI conserva- tively (i.e. requiring positivity on both QFN and TST), which minimizes the chances of misclassification. However, Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152 745 Bolette Søborg et al. Mycobacterium tuberculosis infection in Greenlandic children Research it is possible that earlier TB treatment mitigated the response to QFN and TST in some children33 Finally, the use of information from national registers minimized recall bias, but bias resulting from the non-participation of sick chil- dren cannot be ruled out. Furthermore, the responses to the questionnaire may be subject to recall bias. However, since the study participants did not know their MTI status, any misclassification was non-differential and would, if any- thing, underestimate the true effect of our association with MTI. In conclusion, the present study revealed that family crowding as well as increasing age, Inuit ethnicity, region of residence and age difference between siblings are factors associated with MTI among children in Greenland. However, having had known contact with a person with active TB markedly modified the risk factor profile. Domestic crowding and low maternal educational level emerged as risk factors among children with a known TB contact but not among those who had no known contact with a TB patient. These findings can be used to target future public health in- terventions specifically at Greenlandic children with the highest risk of MTI. ■ Acknowledgements We thank Katrin Kristiansen, Karen Laursen, Jannie Hein Pedersen and her colleagues, Turid Skifte, Melanie Veber and Jette Weismann for their valuable contributions to this study. Finally, we thank the staff at the schools and health- care facilities for their cooperation. Competing interests: None declared. صلخم دنلانيرغ في لافطلأا ينب ةيلسلا ةرطفتلماب ىودعلا راطتخا لماوع دنلانيرغ لافطأ ينب ةيلسلا ةرطفتلماب ىودعلا راطتخا لماوع صحف ضرغلا .ىودعلل راطتخلاا لماوع دشأ ديدحت ضرغل ةرطفتلماب ىودعلا نع فشكلل رابتخا ىرُجأ ،2007 و 2005 يماع ينب ةقيرطلا نع ،ةفلتخم قطانم سمخ في دنلانيرغ في سرادلما في ًلافط 1797 لىع ةيلسلا ىرج دقو .يدلجلا ينلوكربوتلا رابتخاو ،نويرفترنإ-اماغ قلاطنإ سايق قيرط تياذ يرايعم نايبتسا مادختساب لافطلأا ءلاؤه نوعري نم وأ ءابلآل حسم ،نيوبلأا ميلعت ىوتسمو ،لزنلما في ماحدزلاا لوح تايطعلما عمجل ،ةئبعتلا نم ةيفارغويمدلا تايطعلما صلاختسا ًاضيأ ىرجو .لفطلل ةيحصلا ةلاحلاو ةدعابلماو ،ةوخلإا ددعو ،نيوبلأا ةدلاو ناكم لثم -لفط لكل ةماعلا تلاجسلا ،)بركلا في لياتلا ينب ةترفلاو رغصلا في لياتلا ينب ةترفلا( ةوخلإا تادلاو ينب يتسجوللا فّوحتلا مدختساو .لفطلا ةدلاو دنع ملأا رمعو ،ةدلاولا بيترتو ىرج دقو ،ةيلسلا ةرطفتلماب ىودعلاو تايرغتلما هذه ينب تاطابترلاا ةعجارلم .95% ةقثلا تلاصافو ةيحجرلأا بسن قيرط نع جئاتنلا عيمج نع يربعتلا في ةيباجيإ مهصوحف تناك اذإ ةيلسلا ةرطفتلماب ينباصم لافطلأا رابتعا ىرجو .يدلجلا ينلوكربوتلا رابتخاو ،نويرفترنإ-اماغ قلاطنإ سايق رابتخا 8.5% ةيلسلا ةرطفتلماب ىودعلا راشتنلا ليامجلإا لدعلما غلب جئاتنلا لافطلأا نم 26.7% في ةيلسلا ةرطفتلماب ةباصلإا صيخشت متو .)1797/152( لافطأ ةثلاث في 6.4% مب ةنراقم ،لسلاب ينباصم مهل ينطلاخم دوجو مولعلما ةرطفتلماب ةباصلإا لدعم لياجإ ناكو .لسلاب نوباصم نوطلاخم مهيدل سيل :95% ةقثلا ةلصاف ؛4.22 :ةيحجرلأا ةبسن( وميكسلإا لافطأ ينب لىعأ ةيلسلا يذلا خلأا ةدلاو نم ماع نوضغ في نيدولولما لافطلأا ينبو ،)11.5-1.55 .)4.63-1.33 :95% ةقثلا ةلصاف ؛2.48 :ةيجرلأا ةبسن( ةشرابم مهبركي لمشيل مسترلما لسلاب ينباصم ينطلاخم دوجو نع تياذلا غيلبتلا لّدع دقو لافطلأل حجرلأا نم ناكو .ملأا ميلعت ىوتسم ضافخناو لزنلما في ماحدزلاا نأ ةيلسلا ةرطفتلماب ينباصمو ًانس بركأ ينطلاخلم ضرعتلا مهل قبس نيذلا ؛14.2 :ةيحجرلأا ةبسن( ةيلسلا ةرطفتلماب ةباصلإل ةيباجيإ مهصوحف نوكت ةوخلإ اوضرعتي لم نيذلا لافطلأاب ةنراقم )35.0-5.75 :95% ةقثلا ةلصاف .ينباصم ،لزنلما في ينميقلما ددعو ،ةوخلإاب ةقلاعلاو ،يقرعلا لصلأا دعي جاتنتسلاا ينب لسلاب ةباصلإا راطتخاب طبترت يتلا لماوعلا نم تاهملأا ميلعت ىوتسمو ةيلسلا ةرطفتلماب ةباصم ةيلزنم تاعومجم روهظ لديو .دنلانيرغ في لافطلأا .ةسرلأا لخاد ىودعلل ضرعتلا رداصم ةيمهأ لىع 摘要 格陵兰儿童结核杆菌感染的危险因素 目的 旨在调查格陵兰儿童结核杆菌感染（MTI）的危险因 素，从而确定哪些儿童的感染风险最高。 方法 2005到2007年间，对5个不同区域的1797名格陵兰 学龄儿童进行干扰素释放试验（IGRA）和结核菌素试验 （TST），确定其是否存在结核杆菌感染。同时运用标准 化自报问卷对学童父母或监护人进行调查，获取有关家庭 拥挤程度、家长教育水平和儿童健康状况的资料。每位儿 童的人口统计资料可以从公共登记处提取，如父母籍贯、 兄弟姐妹个数、兄弟姐妹年龄距离（上一个或下一个兄弟 姐妹），出生顺序和孩子出生时母亲年龄，。运用逻辑回 归检查这些变量与结核杆菌感染之间的关联，并且所有结 果均以比值比（ORs）和95%可信区间（CIs）表示。如果 儿童干扰素释放试验和结核菌素试验结果均呈阳性，则认 为存在结核杆菌感染。 结果 结核杆菌感染的总发病率为8.5%(152/1797)。与肺 结核患者有接触的儿童中，26.7%被诊断存在结核杆菌感 染，而与肺结核患者没有接触的儿童中，此比例为6.4% 。总体而言，因纽特儿童（比值比：4.22；95%可信区 间：1.55-11.5）和那些与上一个哥或姐的年龄距离不足 一年的儿童(比值比：2.48；95%可信区间：1.33-4.63) 相 比结核杆菌的感染率较高。自我报告的肺结核接触史修正 了原有人口统计资料情况，从而将家庭拥挤程度和母亲教 育水平较低也包括在内。与那些没有受感染的哥哥或姐姐 的儿童相比，有结核杆菌感染阳性的哥哥或姐姐的儿童在 结核杆菌感染测试中更容易呈阳性（比值比：14.2，95% 可信区间：5.75-35.0）。 结论 种族、兄弟姐妹关系、家庭居民数量和母亲的教育水 平是格陵兰儿童肺结核感染相关的危险因素。结核杆菌感 染的强家庭聚集性表明家庭暴露源很重要。 Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152746 Bolette Søborg et al.Mycobacterium tuberculosis infection in Greenlandic children Research Résumé Facteurs de risque d’une infection à Mycobacterium tuberculosis chez les enfants au Groenland Objectif Examiner les facteurs de risque d’une infection à Mycobacterium tuberculosis (MTI) parmi les enfants groenlandais afin d’identifier ceux qui présentent le risque d’infection le plus élevé. Méthodes Entre 2005 et 2007, 1797 écoliers groenlandais de cinq régions différentes ont été testés pour le dépistage de l’infection à MTI au moyen d’un test de détection de l’interféron gamma (IGRA) et d’un test cutané à la tuberculine (TST). Une enquête a été proposée aux parents ou aux tuteurs à l’aide d’un auto-questionnaire standardisé en vue d’obtenir des données sur la composition des ménages, le niveau d’éducation des parents et l’état de santé de l’enfant. Des données démographiques relatives à chaque enfant – à savoir le lieu de naissance des parents, le nombre de frères et sœurs, la différence d’âge entre les frères et sœurs (suivant et précédent), l’ordre de naissance et l’âge de la mère à la naissance de l’enfant – ont également été extraites d’un registre public. Le principe de régression logistique a été appliqué pour vérifier les éventuelles associations entre ces variables et l’infection à MTI. Tous les résultats étaient exprimés en odds-ratios (OR) et en intervalle de confiance à 95% (IC). Les enfants étaient considérés comme atteints de MTI si le test IGRA et le TST étaient tous les deux positifs. Résultats La prévalence globale de l’infection à MTI était de 8,5% (152/1797). On a diagnostiqué une infection à MTI chez 26,7% des enfants ayant été en contact de façon avérée avec une personne atteinte de tuberculose, pour 6,4% d’enfants n’ayant pas eu un tel contact. Globalement, le taux d’infection à MTI était plus élevé chez les enfants inuits (OR: 4,22; IC à 95%: de 1,55 à 11,5) et chez les enfants nés moins d’un an après la naissance de l’enfant précédent (OR: 2,48; IC à 95%: de 1,33 à 4,63). Un contact déclaré avec une personne tuberculeuse modifiait le profil, ainsi qu’un nombre élevé de personnes au foyer et une éducation peu élevée de la mère. Les enfants ayant un frère ou une sœur plus âgé atteint d’une infection à MTI risquaient davantage d’avoir eux-mêmes un résultat positif au dépistage de MTI (OR: 14,2; IC à 95%: de 5,75 à 35.0) que les enfants n’ayant ni frère ni sœur infecté. Conclusion L’ethnicité, les relations avec les frères et sœurs, le nombre de personnes vivant au foyer et le niveau d’éducation maternelle sont des facteurs associés au risque d’infection par la tuberculose parmi les enfants du Groenland. La forte concentration de l’infection à MTI dans les foyers indique que les sources familiales d’exposition sont importantes. Резюме Факторы риска заражения микобактериями туберкулеза у детей в Гренландии Цел ь Ис с ледов ат ь ф а к то ры рис к а з а р а же н и я микобактериями туберкулеза (МБТ) среди гренландских детей с целью выявления пациентов с наивысшим риском заражения. Методы В период с 2005 по 2007 год 1797 школьников из пяти районов Гренландии прошли обследование на заражение МТБ путем проведения анализа секреции гамма-интерферона (IGRA) и туберкулиновой пробы кожи (ТПК). Для получения данных о скученности проживания в домохозяйстве, уровне образования родителей и состоянии здоровья ребенка был проведен опрос родителей или опекунов с использованием стандартной анкеты для самостоятельного заполнения. Кроме того, из государственного реестра были извлечены демографические данные о каждом ребенке: место рождения родителей, число братьев/сестер, период времени между рождениями братьев/ сестер (ближайшего младшего и ближайшего старшего ребенка в семье), очередность рождения и возраст матери при рождении ребенка. Для проверки корреляции между этими переменными и заражением МБТ использовалась логистическая регрессия, а все результаты были выражены в виде отношения шансов (ОШ) и 95%-ного доверительного интервала (ДИ). Считалось, что дети заражены МБТ, если при обследовании у них был получен положительный результат в обоих анализах (IGRA и ТПК). Результаты В целом распространенность инфекции, вызванной заражением МБТ, составляла 8,5% (152/1797). Заражение МБТ было диагностировано у 26,7% детей, о которых было известно, что они контактировали с больным ТБ, и у 6,4% детей, не имевших этого контакта. В целом показатель заболеваемости МБТ был более высоким у инуитских (эскимосских) детей (ОШ: 4,22; 95% ДИ: 1,55–11,5) и у детей, которые родились менее чем через год после рождения ближайшего старшего ребенка в семье (ОШ: 2,48; 95% ДИ: 1,33–4,63). Данные самооценки о контакте с больным ТБ приводили к изменению набора характеристик и включению в него скученности проживания в домохозяйстве и низкого уровня образования матери. У детей, имевших старшего брата/сестру с положительным результатом обследования на заражение МБТ, вероятность положительной реакции в обследованиях на заражение МБТ была значительно выше (ОШ: 14,2; 95% ДИ: 5,75–35,0), чем у детей, не имевших старшего брата/сестру, зараженных МБТ. Вывод Факторами, коррелирующимися с риском заражения ТБ у детей на Гренландии, являются этническая принадлежность, наличие братьев/сестер и уровень образования матери. Интенсивная кластеризация случаев заражения МБТ по домохозяйствам говорит о важности семейных источников экспозиции. Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152 747 Bolette Søborg et al. Mycobacterium tuberculosis infection in Greenlandic children Research Resumen Factores de riesgo de la infección por Mycobacterium tuberculosis en niños de Groenlandia Objetivo Examinar los factores de riesgo de la infección por Mycobacterium tuberculosis (IMT) en niños groenlandeses con el fin de identificar a aquellos están expuestos a un mayor riesgo. Métodos Entre 2005 y 2007, se analizó a 1797 niños en edad escolar de Groenlandia en cinco zonas diferentes para detectar la presencia de la IMT mediante un análisis de liberación de interferón gamma (IGRA, por sus siglas en inglés) y una prueba cutánea de tuberculina (PCT). Los padres o tutores respondieron a un cuestionario autoadministrado y normalizado para obtener datos sobre el número de habitantes del hogar, el nivel educativo de los padres y el estado de salud del niño. También se extrajeron datos demográficos de cada niño de un registro público (es decir, el lugar de nacimiento de los padres, el número de hermanos, la diferencia entre hermanos (entre el que le sigue y el que le precede), el orden de nacimiento y la edad de la madre cuando nació el niño). Se utilizó una regresión logística para comprobar las asociaciones entre estas variables y la IMT. Asimismo, todos los resultados se expresaron como cocientes de probabilidades (CP) e intervalos de confianza (IC) del 95%. Se estableció que los niños tenían la IMT en caso de resultado positivo tanto del análisis IGRA como de la PCT. Resultados La prevalencia global de la IMT fue del 8,5% (152/1797). Se diagnosticó la IMT en el 26,7% de los niños de los que se tenía constancia de un contacto con la tuberculosis, en contraposición con el 6,4% de estos niños que no habían tenido dicho contacto. En general, la tasa de la IMT resultó ser más elevada en niños inuit (CP: 4,22; IC del 95%: 1,55-11,5) y entre niños nacidos menos de un año después del nacimiento del hermano que les precede (CP: 2,48; IC del 95%: 1,33-4,63). La notificación de un contacto con la tuberculosis modificaba el perfil para incluir el número de habitantes del hogar y el bajo nivel educativo de la madre. Los niños que tenían un hermano mayor cuya prueba de IMT fue positiva tenían muchas más probabilidades de que su prueba también ofreciese un resultado positivo (CP: 14,2; IC del 95%: 5,75-35,0) en comparación con los niños que no tenían un hermano mayor infectado. Conclusión La etnia, las relaciones fraternales, el número de habitantes del hogar y el nivel de educación materno son factores asociados al riesgo de sufrir una infección de tuberculosis en niños de Groenlandia. La gran concentración en el hogar de la IMT sugiere que las fuentes familiares de exposición son importantes. References 1. 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Seroprevalence and risk factors for Helicobacter pylori infection in Greenlanders. Helicobacter 2005;10:433–42. doi:10.1111/j.1523- 5378.2005.00351.x PMID:16181354 28. Goodman KJ, Correa P. Transmission of Helicobacter pylori among siblings. Lancet 2000;355:358–62. doi:10.1016/S0140-6736(99)05273-3 PMID:10665555 29. Rieder HL. Epidemiologic basis of tuberculosis control. Paris: International Union Against Tuberculosis and Lung Disease; 1999. 30. Curtis AB, Ridzon R, Vogel R, McDonough S, Hargreaves J, Ferry J et al. Extensive transmission of Mycobacterium tuberculosis from a child. N Engl J Med 1999;341:1491–5. doi:10.1056/NEJM199911113412002 PMID:10559449 31. Marais BJ, Gie RP, Hesseling AH, Beyers N. Adult-type pulmonary tuberculosis in children 10–14 years of age. Pediatr Infect Dis J 2005;24:743–4. doi:10.1097/01.inf.0000173305.04212.09 PMID:16094237 32. The National Greenlandic Tuberculosis Strategy 2007-2012. Nuuk: Chief Medical Officer; 2007. 33. Chee CB, KhinMar KW, Gan SH, Barkham TM, Koh CK, Shen L, et al. Tuberculosis treatment effect on T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens. Eur Respir J 2010.36:355-61 Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152 748A Bolette Søborg et al. Mycobacterium tuberculosis infection in Greenlandic children Research Ta bl e 2. P ot en tia l r is k fa ct or s fo r M yc ob ac te riu m tu be rc ul os is in fe ct io n (M TI ) a m on g 17 97 G re en la nd ic s ch oo lc hi ld re n, 2 00 5– 20 07 Ri sk fa ct or Ch ild re n Ag e- a nd s ex -a dj us te d P Fu lly a dj us te da P W ith ou t M TI W ith M TI OR 95 % C I OR 95 % C I Se x 17 97 15 2 0. 83 0. 93 Fe m al e 90 3 77 0. 96 0. 69 –1 .3 5 – 1. 02 0. 72 –1 .4 2 – M al eb 89 4 75 1 – – 1 – – Ag e (y ea rs ) 17 97 15 2 – – 0. 00 2 – – 0. 01 5– 7b 28 2 19 1 – – 1 Re fe re nc e – 8– 10 50 0 30 1. 01 0. 57 –1 .7 8 – 1. 03 0. 59 –1 .7 7 – 11 –1 3 59 6 49 1. 42 0. 81 –2 .4 8 – 1. 36 0. 80 –2 .3 2 – 14 –1 5 29 6 36 2. 19 1. 24 –3 .8 7 – 2. 19 1. 26 –3 .8 2 – ≥ 16 12 3 18 2. 52 1. 23 –5 .1 6 – 1. 89 0. 94 –3 .8 0 – OR p er a dd iti on al y ea r o f a ge – – 1. 12 1. 05 –1 .1 9 0. 00 03 1. 10 1. 04 –1 .1 7 0. 00 2 Et hn ic ity 17 97 15 2 – – 0. 00 7 – – 0. 00 5 In ui t 15 93 14 8 3. 88 1. 44 –1 0. 5 – 4. 22 1. 55 –1 1. 5 – No n- In ui tb 20 4 4 1 – – 1 – – M ot he r’s a ge (y ea rs ) a t b irt h of s tu dy c hi ld 17 97 15 2 – – 0. 00 9 – – 0. 14 15 –1 9 22 8 29 1. 73 1. 14 –2 .6 1 – 1. 44 0. 88 –2 .3 4 – ≥ 20 b 15 69 12 3 1 – – 1 – – Ty pe o f r es id en ce 16 62 13 6 – – 0. 17 – – 0. 37 Fa m ily b 15 13 11 1 1 – – 1 – – Or ph an ag e, d or m 10 2 18 1. 63 0. 87 –3 .0 3 – 1. 40 0. 75 –2 .6 3 – Fo st er fa m ily 47 7 1. 76 0. 77 –4 .0 0 – 1. 58 0. 68 –3 .7 0 – No . o f a du lts in h ou se ho ld (C F 1) 16 08 12 8 – – 0. 28 – – 0. 43 1– 2b 12 73 10 4 1 – – 1 – – 3+ 33 5 24 0. 72 0. 45 –1 .2 6 – 0. 82 0. 50 –1 .3 4 – Av er ag e no . o f p eo pl e pe r r oo m (C F 2) 14 08 10 0 – – 0. 08 – – 0. 10 < 1 26 8 14 0. 71 0. 36 –1 .4 1 – 0. 84 0. 42 –1 .6 9 – 1– 1. 49 b 61 0 39 1 – – 1 – ≥ 1. 50 53 0 47 1. 44 0. 91 –2 .2 7 – 1. 57 0. 95 –2 .5 8 – St ud y ch ild in o w n ro om (C F 3) 16 53 13 7 – – 0. 23 – – 0. 15 Ye sb 89 4 72 1 – – 1 – – No 75 9 65 1. 28 0. 72 –1 .4 8 1. 33 0. 90 –1 .9 7 Su m o f C Fs c 17 97 15 2 – – 0. 74 – – 0. 76 0 CF b 73 4 61 1 – – 1 – – 1 CF 58 7 54 1. 23 0. 83 –1 .8 3 – 1. 21 0. 81 –1 .8 1 – 2 CF s 39 1 29 1. 04 0. 62 –1 .7 4 – 1. 11 0. 67 –1 .8 6 – 3 CF s 85 8 1. 25 0. 53 –2 .9 3 – 1. 33 0. 61 –2 .9 0 – OR p er a dd iti on al C F – – 1. 05 0. 86 –1 .2 8 0. 63 1. 08 0. 89 –1 .3 1 0. 44 Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152748B Bolette Søborg et al.Mycobacterium tuberculosis infection in Greenlandic children Research Ri sk fa ct or Ch ild re n Ag e- a nd s ex -a dj us te d P Fu lly a dj us te da P W ith ou t M TI W ith M TI OR 95 % C I OR 95 % C I Ag e di ffe re nc e (y ea rs ) w ith n ex t o ld er s ib lin gd 12 35 95 – – 0. 03 – – 0. 03 < 1 (i nc lu di ng tw in ) 61 12 2. 04 1. 00 –4 .1 6 – 2. 08 1. 07 –4 .0 4 – 1b 28 7 25 1 – – 1 – – 2 21 8 10 0. 50 0. 25 –1 .0 1 – 0. 50 0. 24 –1 .0 4 – ≥ 3 66 9 48 0. 83 0. 52 –1 .3 0 – 0. 88 0. 56 –1 .4 0 – M ot he r’s e du ca tio n 11 04 75 – – 0. 33 – – 0. 31 8t h gr ad e an d no fu rth er s ch oo lin g 11 7 12 1. 26 0. 53 –3 .0 0 – 1. 61 0. 69 –3 .7 8 – 8t h gr ad e an d sk ille d la bo ur 24 3 18 1. 09 0. 56 –2 .1 0 – 1. 04 0. 53 –2 .0 2 – 10 th g ra de a nd s ki lle d la bo ur b 49 2 35 1 – – 1 – – 10 th g ra de , 3 y ea rs v oc at io na l t ra in in g & co ur se s an d ba ch el or ’s d eg re ee 6 1 2. 80 0. 40 –1 9. 5 – 1. 84 0. 18 –1 8. 7 – Hi gh s ch oo l a nd s ki lle d la bo ur 15 4 5 0. 43 0. 17 –1 .0 8 – 0. 41 0. 15 –1 .1 1 – Hi gh s ch oo l a nd b ac he lo r’s /m as te r’s d eg re e 92 4 0. 65 0. 22 –1 .9 0 – 0. 71 0. 24 –2 .0 9 – OR p er a dd iti on al le ve l o f m at er na l e du ca tio n – – 0. 83 0. 6– 1. 03 0. 09 0. 80 0. 64 –1 .0 1 0. 06 Re gi on 17 97 15 2 – – < 0 .0 00 1 – – < 0 .0 00 1 Ea st b 36 7 28 1 – – 1 – – So ut h 11 00 11 8 1. 44 0. 90 –2 .3 2 – 1. 51 0. 94 –2 .4 2 – W es t 42 0 6 0. 18 0. 07 –0 .4 4 – 0. 20 0. 08 –0 .4 8 – BM I ( kg /c m 2 )f 17 77 14 8 – – 0. 63 0. 49 Un de rw ei gh t 16 1 1. 13 0. 24 –5 .3 3 – 1. 83 0. 31 –1 0. 7 – No rm al b 13 98 11 1 1 – – 1 – – Ov er w ei gh t 29 5 25 0. 97 0. 61 –1 .5 3 – 0. 95 0. 60 –1 .5 0 – Ob es e 68 11 1. 58 0. 77 –3 .2 2 – 1. 69 0. 78 –3 .6 5 – Ob es e (m ea su re d by B M I)g 17 77 14 8 – – 0. 20 – – 0. 16 No b 17 09 13 7 1 – – 1 – – Ye s 68 11 1. 59 0. 79 –3 .2 1 – 1. 71 0. 80 –3 .6 6 – BM I, bo dy m as s in de x; C F, cr ow di ng fa ct or ; C I, co nfi de nc e in te rv al ; O R, o dd s ra tio . a A dj us te d fo r s ex , a ge , e th ni ci ty, m ot he r’s a ge , r eg io n an d di ffe re nc e in a ge b et w ee n st ud y ch ild a nd n ex t o ld er s ib lin g. b R ef er en ce c at eg or y. c T he s um o f t he C Fs w as o bt ai ne d by a dd in g th e th re e CF s gi ve n in th e ta bl e, a s fo llo w s: C F 1 w as a dd ed w he n 3 or m or e ad ul ts li ve d in th e ho us eh ol d; C F 2, w he n th e av er ag e nu m be r o f p eo pl e pe r r oo m w as a t l ea st 1 .5 ; a nd C F 3, w he n th e st ud y ch ild d id n ot h av e th ei r o w n ro om . d S ub an al ys is fo r < 1 y ea r d iff er en ce v er su s ≥ 1 ye ar d iff er en ce b et w ee n th e ag e of th e st ud y ch ild a nd th at o f t he n ex t o ld er s ib lin g: O R = 2 .4 8 (9 5% C I: 1. 33 –4 .6 3) . e I ns te ad o f q ua lif yin g fo r e nt ra nc e to a b ac he lo r’s p ro gr am m e th ro ug h th re e ye ar s of u pp er s ec on da ry s ch oo l, ch ild re n in D en m ar k an d Gr ee nl an d ca n qu al ify fo r e nt ra nc e by c om pl et in g th re e ye ar s of c er tifi ed v oc at io na lly o rie nt ed tr ai ni ng a nd c ou rs es . f B M I c at eg or ie s w er e de fin ed a cc or di ng to a ge - an d se x- sp ec ifi c pe rc en til es e va lu at ed b y Ce nt er s fo r D is ea se C on tro l a nd P re ve nt io n BM I-f or -a ge g ro w th c ha rts fo r g irl s an d bo ys . D efi ni tio ns w er e as fo llo w s: u nd er w ei gh t, < 5 th p er ce nt ile ; n or m al w ei gh t, 5t h pe rc en til e to < 8 5t h pe rc en til e; o ve rw ei gh t, 85 th p er ce nt ile to < 9 5t h pe rc en til e; o be se , ≥ 9 5t h pe rc en til e. g O be si ty w as d efi ne d as in p re vio us fo ot no te ; u nd er w ei gh t, no rm al w ei gh t a nd o ve rw ei gh t w er e co m bi ne d in to a s in gl e ca te go ry . Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152 748C Bolette Søborg et al. Mycobacterium tuberculosis infection in Greenlandic children Research Ta bl e 3. O dd s ra tio s (O Rs ) f or M yc ob ac te riu m tu be rc ul os is in fe ct io n (M TI ), by p ot en tia l r is k fa ct or s, a m on g 17 97 G re en la nd ic s ch oo lc hi ld re n st ra tifi ed b y TB c on ta ct Po te nt ia l r is k fa ct or W ith ou t k no w n TB c on ta ct W ith k no w n TB c on ta ct Te st fo r e ffe ct m od ifi - ca tio n of T B co nt ac t Ch ild re n OR 95 % C I P Ch ild re n OR 95 % C I P P No . W ith M TI No . W ith M TI Se x 16 17 10 4 – – 0. 76 18 0 48 – – 0. 55 0. 50 Fe m al e 81 2 50 0. 94 0. 62 –1 .4 1 – 91 27 1. 24 0. 61 –2 .5 2 – – M al ea 80 5 54 1 – – 89 21 1 – – – Ag e (y ea rs ) 16 17 10 4 – – 0. 00 2 18 0 48 – – 0. 29 – 5– 7a 24 9 9 1 – – 33 10 1 – – – 8– 10 44 9 21 1. 43 0. 71 –2 .8 9 – 51 9 0. 86 0. 26 –2 .8 0 – – 11 –1 3 53 4 29 1. 55 0. 76 –3 .1 4 – 62 20 1. 85 0. 56 –6 .0 7 – – 14 –1 5 27 2 28 3. 14 1. 55 –6 .3 6 – 24 8 2. 10 0. 55 –7 .9 5 – – ≥ 16 11 3 17 3. 30 1. 43 –7 .6 1 – 10 1 0. 33 0. 03 –3 .9 4 – – OR p er e ac h ad di tio na l y ea r o f a ge – – 1. 14 1. 06 –1 .2 3 0. 00 03 – – 1. 05 0. 92 –1 .2 0 0. 45 0. 29 c Et hn ic ity 16 17 10 4 – – 0. 03 18 0 48 – – 0. 03 0. 44 In ui t 14 39 10 1 3. 55 1. 15 –1 1. 0 – 15 4 47 8. 53 1. 19 –6 1. 4 – – No n- In ui ta 17 8 3 1 – – 26 1 1 – – – M ot he r’s a ge (y ea rs ) a t b irt h of s tu dy c hi ld 16 17 10 4 – – 0. 24 18 0 48 – – 0. 12 0. 32 15 –1 9 20 5 20 1. 39 0. 80 –2 .4 0 – 23 9 2. 70 0. 78 –9 .2 8 – – ≥ 20 a 14 12 84 1 – – 15 7 39 1 – – – Ty pe o f r es id en ce 14 88 88 – – 0. 44 17 4 48 – – 0. 68 0. 89 Fa m ily d w el lin ga 13 55 69 1 – – 15 8 42 1 – – – Or ph an ag e, d or m 93 14 1. 28 0. 60 –2 .7 5 – 9 4 2. 00 0. 34 –1 1. 6 – – Fo st er fa m ily 40 5 1. 84 0. 69 –4 .9 0 – 7 2 1. 60 0. 17 –1 5. 0 – – No . o f a du lts in h ou se ho ld (C F 1) 14 37 81 – – 0. 06 17 1 47 – – 0. 15 0. 02 1– 2a 11 33 71 1 – – 14 0 33 1 – – – 2+ 30 4 10 0. 50 0. 24 –1 .0 2 31 14 2. 18 0. 76 –6 .2 5 – – Av er ag e no . o f p eo pl e pe r r oo m (C F 2) 12 66 60 – – 0. 77 14 2 40 – – 0. 57 – < 1 24 4 10 0. 85 0. 39 –1 .8 3 – 24 4 0. 98 0. 21 –4 .5 7 – – 1– 1. 49 a 55 6 27 1 – – 54 12 1 – – – ≥ 1. 50 46 6 23 1. 15 0. 59 –2 .2 6 – 64 24 1. 62 0. 62 –4 .1 8 – – OR p er e ac h ad di tio na l c at eg or y – – 1. 17 0. 7– 1. 77 0. 47 – – 1. 37 0. 68 –2 .7 9 0. 38 0. 71 c St ud y ch ild in o w n ro om (C F 3) 14 82 89 – – 0. 64 17 1 48 – – 0. 26 0. 48 Ye sa 80 7 53 1 – – 87 19 1 – – – No 67 5 36 1. 13 0. 69 –1 .8 4 – 84 29 1. 57 0. 71 –3 .4 5 – – Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152748D Bolette Søborg et al.Mycobacterium tuberculosis infection in Greenlandic children Research Po te nt ia l r is k fa ct or W ith ou t k no w n TB c on ta ct W ith k no w n TB c on ta ct Te st fo r e ffe ct m od ifi - ca tio n of T B co nt ac t Ch ild re n OR 95 % C I P Ch ild re n OR 95 % C I P P No . W ith M TI No . W ith M TI Su m o f C Fs b 16 17 10 4 – – 0. 45 18 0 48 – – 0. 11 – 0 CF sa 66 6 52 1 – – 68 9 1 – – – 1 CF 52 9 36 0. 95 0. 60 –1 .5 1 – 58 18 2. 82 1. 04 –7 .6 0 – – 2 CF s 35 0 15 0. 72 0. 38 –1 .3 7 – 41 14 2. 52 0. 89 –7 .1 6 – – 3 CF s 72 1 0. 28 0. 04 –1 .8 1 – 13 7 4. 24 1. 04 –1 7. 3 – – OR p er e ac h ad di tio na l C F – – 0. 82 0. 64 –1 .0 6 0. 13 – – 1. 54 1. 00 –2 .3 0 0. 03 0. 00 9c Ag e di ffe re nc e (y ea rs ) w ith n ex t o ld er s ib lin g 11 13 62 – – 0. 19 12 2 33 – – 0. 17 0. 90 < 1 (i nc lu di ng tw in ) 52 7 1. 80 0. 74 –4 .4 2 – 9 5 3. 47 0. 90 –1 3. 3 – – 1a 25 6 17 1 – – 31 8 1 – – – 2 19 7 6 0. 47 0. 19 –1 .1 6 – 21 4 0. 56 0. 11 –2 .8 4 – – ≥ 3 60 8 32 0. 90 0. 52 –1 .5 8 – 61 16 1. 04 0. 35 –3 .0 4 – – M ot he r’s e du ca tio n 97 7 45 – – 0. 57 12 7 30 – – 0. 01 – 1: 8 th g ra de a nd n o fu rth er s ch oo lin g 10 0 4 0. 84 0. 20 –3 .5 1 – 17 8 3. 92 1. 21 –1 2. 7 – – 2: 8 th g ra de a nd s ki lle d la bo ur 21 5 11 0. 96 0. 39 –2 .3 2 – 28 7 0. 87 0. 21 –3 .5 9 – – 3: 1 0t h gr ad e an d sk ille d la bo ur a 42 7 22 1 – – 65 13 1 – – – 4: 1 0t h gr ad e, 3 y ea rs v oc at io na l t ra in in g & co ur se s, a nd ba ch el or ’s d eg re e d 5 1 3. 25 0. 39 –2 7. 4 – 1 0 – – – – 5: H ig h sc ho ol a nd s ki lle d la bo ur 14 2 3 0. 37 0. 11 –1 .2 7 – 12 2 0. 41 0. 09 –1 .9 6 – – 6: H ig h sc ho ol a nd b ac he lo r’s /m as te r’s d eg re e 88 4 1. 03 0. 34 –3 .1 0 – 4 0 – – – – OR p er e ac h ad di tio na l e du ca tio n le ve l – – 0. 93 0. 71 –1 .2 0 0. 56 – – 0. 55 0. 34 –0 .8 8 0. 01 0. 05 c Re gi on 16 17 10 4 – – 0. 00 02 18 0 48 – – 0. 97 0. 03 Ea st a 33 1 19 1 – – 36 9 1 – – – So ut h 88 0 83 1. 58 0. 91 –2 .7 5 – 13 0 35 1. 15 0. 42 –3 .1 6 – – W es t 40 6 2 0. 09 0. 02 –0 .4 0 – 14 4 1. 10 0. 21 –5 .7 1 – – BM Ie 15 99 10 1 – – 0. 03 17 8 47 – – 0. 62 – Un de rw ei gh t 14 1 3. 11 0. 43 –2 2. 7 – 2 0 – – – – No rm al a 12 60 76 1 – – 13 8 35 1 – – – Ov er w ei gh t 26 2 14 0. 74 0. 42 –1 .3 1 – 14 4 0. 61 0. 08 –4 .4 5 – – Ob es e 63 10 2. 52 1. 07 –5 .9 1 – 5 1 1. 10 0. 38 –3 .1 7 – – Bull World Health Organ 2011;89:741–748E | doi:10.2471/BLT.10.084152 748E Bolette Søborg et al. Mycobacterium tuberculosis infection in Greenlandic children Research Po te nt ia l r is k fa ct or W ith ou t k no w n TB c on ta ct W ith k no w n TB c on ta ct Te st fo r e ffe ct m od ifi - ca tio n of T B co nt ac t Ch ild re n OR 95 % C I P Ch ild re n OR 95 % C I P P No . W ith M TI No . W ith M TI OR p er in cr ea se in B M I c la ss – – 1. 15 0. 76 –1 .7 5 0. 51 – – 1. 14 0. 50 –2 .3 8 0. 72 0. 99 c Ob es e (m ea su re d by B M I)f 15 99 10 1 – – 0. 02 17 8 47 – – 0. 62 0. 19 No a 15 36 91 1 – – 17 3 46 1 – – – Ye s 63 10 2. 51 1. 09 –5 .7 8 – 5 1 0. 63 0. 10 –4 .0 1 – – BM I, bo dy m as s in de x; C F, cr ow di ng fa ct or ; C I, co nfi de nc e in te rv al . Th e es tim at es w er e fu lly a dj us te d fo r t he fo llo w in g va ria bl es : s ex , a ge , e th ni ci ty, m ot he r’s a ge a t b irt h of s tu dy c hi ld , r eg io n an d ag e di ffe re nc e be tw ee n st ud y ch ild a nd n ex t o ld er s ib lin g. a R ef er en ce c at eg or y. b T he s um o f t he C Fs w as o bt ai ne d by a dd in g th e th re e CF s gi ve n in th e ta bl e, a s fo llo w s: C F 1 w as a dd ed w he n 3 or m or e ad ul ts li ve d in th e ho us eh ol d; C F 2, w he n th e av er ag e nu m be r o f p eo pl e pe r r oo m w as a t l ea st 1 .5 ; a nd C F 3, w he n th e st ud y ch ild di d no t h av e th ei r o w n ro om . c I nt er ac tio n te st p er fo rm ed a s te st fo r h om og en ei ty o f t re nd s. d I ns te ad o f q ua lif yin g fo r e nt ra nc e to a b ac he lo r’s p ro gr am m e th ro ug h th re e ye ar s of u pp er s ec on da ry s ch oo l, a pe rs on in D en m ar k an d Gr ee nl an d ca n qu al ify fo r e nt ra nc e by c om pl et in g th re e ye ar s of c er tifi ed v oc at io na lly o rie nt ed tr ai ni ng a nd c ou rs es . e B M I c at eg or ie s w er e de fin ed a cc or di ng to a ge - a nd s ex -s pe ci fic p er ce nt ile s ev al ua te d by C en te rs fo r D ise as e Co nt ro l a nd P re ve nt io n BM I-f or -a ge g ro w th c ha rts fo r g irl s an d bo ys . D efi ni tio ns w er e as fo llo w s: u nd er w ei gh t, < 5 th p er ce nt ile ; n or m al w ei gh t, 5t h pe rc en til e to < 8 5t h pe rc en til e; o ve rw ei gh t, 85 th p er ce nt ile to < 9 5t h pe rc en til e; o be se , ≥ 9 5t h pe rc en til e. f O be sit y w as d efi ne d as in p re vio us fo ot no te ; u nd er w ei gh t, no rm al w ei gh t a nd o ve rw ei gh t w er e co m bi ne d in to a s in gl e ca te go ry .