Baussano, I.

Borraccino, Alberto

Bugiani, M.

Carosso, A.

Migliore, E.

Piccioni, P.

English

Institutional Research Information System University of Turin

The contribution of diabetes is still widely overlooked in TBprevention efforts [1]. In this sample of Greenland Inuit whereboth HIV and undernutrition remain uncommon, the risk ofdeveloping TB was markedly higher in persons with co-existingdiabetes than in persons without. The very high risk associatedwith diabetes suggests potential reduction in the Greenland TBincidence rates through incorporating diabetes control andprevention in TB prevention schemes. However, the validity ofthe results should be confirmed in a larger sample size, pre-ferentially by applying longer follow-up time to the study cohort.Stine Byberg*, Bolette Soborg#, Mikael Andersson",Peter Bjerregaard+ and Marit E. Jørgensen**Epidemiology group, Steno Diabetes Center A/S, Gentofte,#Department of Infectious Disease Epidemiology, StatensSerum Institut, "Department of Epidemiology Research,Statens Serum Institut, and +Centre of Health Research inGreenland, National Institute of Public Health, University ofSouthern Denmark, Copenhagen Denmark.Correspondence: S. Byberg, Epidemiology Group, StenoDiabetes Center A/S, Niels Steensensvej 2-4, DK-2820, Gentofte,Denmark. E-mail: stinebyberg@gmail.comStatement of Interest: None declared.Acknowledgements: The present study received funding fromthe Commission of Scientific Research in Greenland (Nuuk,Greenland). The B99 and IHIT studies were funded by the DanishMedical Research Council and Karen Elise Jensen’s Foundation.REFERENCES1 Jeon CY, Murray MB. Diabetes mellitus increases the risk of activetuberculosis: a systematic review of 13 observational studies. PLoSMed 2008; 5: e152.2 Jørgensen ME, Bjerregaard P, Borch-Johnsen K. Diabetes andimpaired glucose tolerance among the inuit population ofGreenland. Diabetes Care 2002; 25: 1766–1771.3 Soborg B, Koch A, Thomsen VØ, et al. Ongoing tuberculosistransmission to children in Greenland. Eur Resp J 2010; 36: 878–884.4 Bjerregaard P. Greenland survey 2005–2010. Population sampleand survey methods. 2nd Edn. www.si-folkesundhed.dk/upload/inuit_health_in_transition_greenland_methods_5_2nd_revision.pdfDate last updated: 2011. Date last accessed: September 12, 2011.5 Søborg C, Søborg B, Puoelsen S, et al. Doubling of the tuberculosisincidence in Greenland over an 8-years period (1990–1997). Int JTuberc Lung Dis 2001; 5: 257–265.6 Ponce-De-Leon A, Garcia-Garcia MAL, Garcia-Sancho MAC.Tuberculosis and diabetes in Southern Mexico. Diabetes Care2004; 27: 1584–1590.7 Mori MA, Leonardson G, Welty TK. The benefits of isoniazidchemoprophylaxis and risk factors for tuberculosis among OglalaSioux Indians. Arch Intern Med 1992; 152: 550.8 Ladefoged K, Rendal T, Skifte T, et al. Risk factors for tuberculosisin Greenland: case-control study. Int J Tuberc Lung Dis 2011; 15:44–49.9 Leegaard A, Riis A, Kornum JB, et al. Diabetes, glycemic control,and risk of tuberculosis. Diabetes Care 2011; 34: 2530–2535.10 Søborg B, Andersen AB, Larsen HK, et al. Detecting a lowprevalence of latent tuberculosis among health care workers inDenmark detected by M. tuberculosis specific IFN-c whole-bloodtest. Scand J Infect Dis 2007; 39: 554–559.DOI: 10.1183/09031936.00039612Outcomes of a tuberculosis contact investigationprogramme in ItalyTo the Editors:Mycobacterium tuberculosis transmission is affected by severalkey factors, such as contagiousness of the index tuberculosis(TB) case, immune status and susceptibility of the exposed TBcontact, duration and patterns of contact between the index TBcase and the exposed TB contact, and characteristics of theenvironment within which such contact occurs [1–3]. Tracingstrategies that allow the early identification and appropriatetreatment of TB contacts with latent TB infection (LTBI) oractive TB should be a priority of TB control programmes withadequate resources [3, 4].In agreement with the guidelines laid out by the Italian Ministryof Health, the Piedmont Region has activated and regularlyupdated TB contact investigation procedures [5]. We used datafrom the Piedmont Region TB contact investigation programme toassess the role of selected risk factors for TB infection (TBI) amongTB contacts in the city of Turin, Italy. For each suspected orconfirmed pulmonary TB case, active contact investigation wasconducted among household members, close contacts and regularcontacts, defined according to the stone-in-the-pond method [6].Passive investigation was used for occasional contacts [5].The Piedmont TB notification systems were used to identifypulmonary TB cases between January 2002 and December 2008.TB cases were classified into three categories of contagious-ness: 1) sputum smear-positive and culture-positive (acid-fastbacillus positive (AFB+)); 2) sputum smear-negative but culture-positive (CULT+); and 3) sputum smear-negative and culture-negative or not examined, i.e. other than defined (OtD).Interviews were conducted with each TB case to identify TBcontacts, defined as anyone having shared air with an active TBcase. All traced TB contacts were screened for active TB or LTBIusing the tuberculin skin test (TST). The TST was performedusing tuberculin purified protein derivative (5 IU) according tothe Mantoux method [3]. TB contacts were classified as infectedeither if the induration was o5 mm in diameter regardless ofany prior bacille Calmette–Gue´rin (BCG) vaccination [3] or ifclinical, bacteriological or radiological signs or symptoms ofmanifest disease were present. If the TST was negative, a second cEUROPEAN RESPIRATORY JOURNAL VOLUME 40 NUMBER 5 1291TST was performed 6–8 weeks later, and that result wasconsidered final and used in the present analyses [5].TB contacts were then categorised according to the closeness ofcontact with the index TB case: household contacts (those livingin the same house as the index TB case, e.g. relatives), regularcontacts (those who had regular prolonged contact with theindex TB case or who spent time with them in a confined space,e.g. friends and colleagues) and occasional contacts (those whoshared air with the index TB case for ,12 h or who spent timewith them in an unconfined space) [5].To account for any expected effect of age on risk of TBI, we testedthe nonlinearity of the relationship between age and TST positivityin TB contacts by fitting an unrestricted cubic spline with fourknots in a logistic regression model including contagiousness, ageand sex of index TB cases, and age, sex, place of birth of TBcontacts, and closeness of contact with the index TB case.Logistic regression was performed in a multilevel analysis toevaluate the predictors of TBI, considering the effect of clusterby TB case. The first level included the characteristics of theindex case (contagiousness, age and sex) and the second levelincluded the characteristics of the TB contact (closeness ofcontact, age, place of birth and sex). We evaluated the statistical0.51.00.0-0.5-1.0-1.5-2.0Log oddsAge of TB contacts yrs0 20 40 60 80 100FIGURE 1. Log odds of tuberculin skin test (TST) positivity (––––) with 95%confidence intervals (- - - -) in evaluated tuberculosis (TB) contacts by age, adjustedfor contagiousness, age and sex of the index TB case, and age, sex, place of birthand closeness of contact of TB contacts. TST positivity was defined as tuberculinpurified protein derivative reaction of o5 mm.TABLE 1 Results of multilevel analysis for the association between determinants of tuberculosis (TB) infection and activepulmonary TB# in evaluated contacts overall, and by age of TB contactOverall OR (95% CI) Age of TB contactsf35 yrs .35 yrsSubjects n OR (95% CI) Subjects n OR (95% CI)First levelContagiousness of index TB caseOtD 1.00 352 1.00 340 1.00CULT+ 2.93 (1.34–6.41) 253 2.08 (1.09–3.94) 360 0.82 (0.53–1.27)AFB+ 3.03 (1.73–5.32) 1568 2.46 (1.54–3.93) 1347 1.20 (0.87–1.66)Age of the index TB case 0.99 (0.99–1.00) 0.98 (0.97–0.99) 1.00 (0.99–1.01)Males 1.00 1201 1.00 1080 1.00Females 0.95 (0.75–1.19) 972 1.01 (0.71–1.44) 867 0.98 (0.76–1.25)Second levelCloseness of contactOccasional 1.00 61 1.00 60 1.00Regular 1.08 (0.59–1.99) 345 2.51 (0.85–7.40) 324 0.50 (0.22–1.14)Household 1.53 (0.86–2.71) 1767 4.78 (1.69–13.50) 1563 0.66 (0.30–1.43)Age of TB contact 1.05 (1.04–1.06) 1.08 (1.07–1.10) 1.01 (1.00–1.02)Place of birth of TB contactItaly 1.00 1296 1.00 1472 1.00Elsewhere 5.22 (4.20–6.49) 837 4.79 (3.55–6.47) 395 4.82 (3.47–6.69)Sex of TB contactMale 1.00 1099 1.00 838 1.00Female 0.76 (0.65–0.90) 1068 0.85 (0.67–1.09) 1106 0.64 (0.52–0.80)OtD: other than defined, i.e. both sputum smear and culture negative or missing, but clinically and/or radiologically diagnosed as being compatible with TB; CULT+:sputum smear examination negative but sputum culture positive for Mycobacterium tuberculosis complex; AFB+: acid-fast bacillus positive, i.e. sputum smearexamination positive for acid-fast bacilli and culture positive for M. tuberculosis complex. #: a positive tuberculin skin test was defined as tuberculin purified proteinderivative reaction of o5 mm.1292 VOLUME 40 NUMBER 5 EUROPEAN RESPIRATORY JOURNALsignificance of the interactions between the index TB case andthe TB contact characteristics. Odds ratios with 95% confidenceintervals were used as a measure of association.A total of 833 index TB cases with at least one contact wereidentified; 4,441 contacts were screened using the TST and 3,942(82.8%) were evaluated. The prevalence of TBI among contactswas 45.0% (1,773 TB contacts had an intradermal reactiono5 mm). 28 (0.7%) contacts were found to have active TB.The nonlinearity test showed that the age, adjusted for con-tagiousness, age and sex of the index TB case, and age, sex, placeof birth and closeness of contact of TB contacts, was positively andstrongly associated with TBI in TB contacts until ,35 yrs of age,after which the log-relative risk increased with a much lower slope(fig. 1). Therefore, we stratified age into two categories, below andabove the inflection point at 35 yrs of age (f35 and .35 yrs).Results of the multilevel analysis, overall and stratified by ageof TB contacts, are shown in table 1. Laboratory and clinicalresults, which were used as an indicator of contagiousness, weresignificantly associated with the TBI status of contacts: overall,the contacts of both AFB+ and CULT+ cases had a statisticallysignificantly higher risk of TBI than did the contacts of OtDcases (OR 3.03 (95% CI 1.73–5.32) and OR 2.93 (95% CI 1.34–6.41), respectively). The strength of the association was greaterin the age groupf35 yrs compared with.35 yrs (OR 2.46 (95%CI 1.54–3.93) and OR 2.08 (95% CI 1.09–3.94) in the contacts ofAFB+ and CULT+ cases, respectively). Closeness of contact wasa predictor of TBI, even though the association was statisticallysignificant only in the age group f35 yrs, in which householdcontacts had a significantly higher risk of TBI than occasionalcontacts (OR 4.78, 95% CI 1.69–13.50) (table 1).As expected, contagiousness and closeness of contact were themajor determinants of LTBI and active TB risk [7–9]. However,these factors seemed to play a different role depending on theage of the TB contact. In particular, among TB contactsf35 yrsof age, household contacts and contacts of AFB+ cases displayedthe highest risk of TBI. We also found that the contacts of CULT+cases had a high risk of infection, despite the fact that CULT+cases are expected to be less contagious than AFB+ cases due toa lower bacterial load.In TB contacts aged .35 yrs, the effects of the main risk factorsfor tuberculin conversion, contagiousness and closeness ofcontact, apparently disappear, as confirmed by the significantinteraction found between the age of TB contacts and the maindeterminants of TBI, while the effect of place of birth of TBcontacts and the cohort effect persisted. It is possible that in theolder age group and in foreign-born TB contacts, incident TBIwas hidden by a higher prevalence of previous infections. As aconsequence, the likelihood of finding true incident TBI washigher in TB contactsf35 yrs of age. Furthermore, the apparentprotective effect of being born in Italy could be due to a higherprevalence of previous TBI in foreign TB contacts born incountries with high TB prevalence.The operative meaning of this finding is that a number of TBcontacts in the older age group, even if they were candidatesfor LTBI treatment, did not appear to have new TBI. For thisreason, it may be suggested that low priority should be givento the treatment of subjects .35 yrs of age. This is particularlytrue for BCG-vaccinated subjects, and for subjects born incountries with high TB prevalence.In conclusion, our results suggest that TB contact investigationprogrammes should be expanded to include contacts ofCULT+ cases and regular TB contacts, especially if an outbreakis demonstrated in household contacts. Finally, due to theobserved increased risk of TBI, which is likely to be recent, TBcontact investigation efforts should be maximised in thepopulation aged f35 yrs.Enrica Migliore*,e, Alberto Borraccino#,e, Iacopo Baussano",+,Pavilio Piccioni1, Aurelia Carosso1 and Massimiliano Bugiani1*Cancer Epidemiology Unit, ASO San Giovanni BattistaHospital and CPO Piemonte, #Dept of Public Health Scienceand Pediatrics, University of Turin, 1Unit of Pneumology,National Local Health – ASL TO2, Turin, and "CancerEpidemiology Unit, UPO ‘‘A. Avogadro’’ and CPO Piemonte,Novara, Italy. +Dept of Infectious Disease Epidemiology, StMary’s Campus, Imperial College, London, UK. eBoth authorscontributed equally to this work.Correspondence: A. Borraccino, Dept of Public Health Scienceand Pediatrics, University of Turin, Via Santena 5bis, 10126Turin, Italy. E-mail: alberto.borraccino@unito.itSupport Statement: This study was partially supported by thePiedmont Region (Ricerca Sanitaria Finalizzata, years 2002 and2008).Statement of Interest: None declared.REFERENCES1 Dye C, Lonnroth K, Jaramillo E, et al. Trends in tuberculosisincidence and their determinants in 134 countries. Bull World HealthOrgan 2009; 87: 683–691.2 Baussano I, Nunn P, Williams B, et al. Tuberculosis among healthcare workers. Emerg Infect Dis 2011; 17: 488–494.3 Centers for Disease Control. Guidelines for the investigation ofcontacts of persons with infectious tuberculosis. Recommendationsfrom the National Tuberculosis Controllers Association and CDC.MMWR Recomm Rep 2005; 54: 1–47.4 British Thorax Society. Control and prevention of tuberculosis inthe United Kingdom: code of practice 2000. Joint TuberculosisCommittee of the British Thoracic Society. Thorax 2000; 55: 887–901.5 Piedmont Region. Protocollo per il controllo della TB umana inPiemonte [Protocol for the control of human TB in Piedmont]. DRG31/27361. Turin, Regione Piemonte, 1998.6 Veen J. Microepidemics of tuberculosis: the stone-in-the-pondprinciple. Tuber Lung Dis 1992; 73: 73–76.7 Reichler MR, Reves R, Bur S, et al. Evaluation of investigationsconducted to detect and prevent transmission of tuberculosis. JAMA2002; 287: 991–995.8 Aissa K, Madhi F, Ronsin N, et al. Evaluation of a model for efficientscreening of tuberculosis contact subjects. Am J Respir Crit Care Med2008; 177: 1041–1047.9 Moran-Mendoza O, Marion SA, Elwood K, et al. Risk factorsfor developing tuberculosis: a 12-year follow-up of contacts oftuberculosis cases. Int J Tuberc Lung Dis 2010; 14: 1112–1119.DOI: 10.1183/09031936.00047312 cEUROPEAN RESPIRATORY JOURNAL VOLUME 40 NUMBER 5 1293

Outcomes of a tuberculosis contact investigation program in Italy

https://iris.unito.it/bitstream/2318/121540/1/Migliore%202012%20Eur%20Respir%20J.pdf

Outcomes of a tuberculosis contact investigation program in Italy

Abstract

Similar works

Full text

Available Versions

Institutional Research Information System University of Turin