Assessing the Impact of Targeted Tuberculosis Interventions

Correspondence 557 and colleagues describe measuring particulate matter with a diameter of 2.5 mm or less, expressed as mg/m3, using a DustTrak monitor (TSI, Inc., Shoreview, MN) (1). The DustTrak instrument is a light scattering monitor which estimates the total mass concentration of a source by counting the total number of particles and then multiplying the result by a uniform particle mass. However, the mass concentrations calculated by this instrument are generated with the assumption that all particles are of uniform size and mass. Because particle volumes and weights can vary depending on the source from which they were generated, determining the mass concentration for all particles with this assumption can generate erroneous estimates. To correct for this limitation, the authors should have calibrated the concentrations calculated by the DustTrak monitor to those generated by an integrated filter mass collection unit in both the indoor and outdoor settings. The ‘‘calibration factor’’ the authors cited and used in their investigation may have been appropriate for the referenced studies (2, 3), but it may not have been correct for either the indoor or outdoor sources in their investigation. The appropriate calibration factor for the DustTrak monitor can only be established through serial side-by-side comparisons against gravimetric samplers. The authors’ report of high intermachine reliability between two DustTrak monitors establishes that the measurements of the monitors were precise; however, for the reason delineated above, it does not confirm that the measurements were accurate. Conflict of Interest Statement: The author has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. WARE G. KUSCHNER U.S. Department of Veterans Affairs Palo Alto Health Care System Palo Alto, California References 1. Osman LM, Douglas JG, Garden C, Reglitz K, Lyon J, Gordon S, Ayres JG. Indoor air quality in homes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176:465–472. 2. Vojta PJ, Friedman W, Marker DA, Clickner R, Rogers JW, Viet SM, Muilenberg ML, Thorne PS, Arbes SJ Jr, Zeldin DC. First National Survey of Lead and Allergens in Housing: survey design and methods for the allergen and endotoxin components. Environ Health Perspect 2002;110:527–532. 3. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation: the St. George’s Respiratory Questionnaire. Am Rev Respir Dis 1992;145:1321–1327. From the Authors: Dr. Kuschner points out that the calibration factor we used in our article investigating the relationship of health status to indoor fine particle levels (1) may have been appropriate for the studies we referenced, but may not have been correct for our sources. We have realized that the reference numbers are incorrect in the Methods of the main paper, and this section should refer to the references cited herein (2, 3), which are those in the online Methods supplement. This may in part answer Dr. Kuschner’s concern. More generally, use of a different calibration factor would not influence the relationship between increasing PM2.5 concentration and decreasing health status. The studies we quote for calibration were undertaken in indoor environments, and we think it is reasonable to believe that sources of particles are similar to those present in the homes we monitored. Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. LIESL M. OSMAN JON G. AYRES Liberty Safe Work Research Centre Aberdeen, United Kingdom References 1. Osman LM, Douglas JG, Garden C, Reglitz K, Lyon J, Gordon S, Ayres JG. Indoor air quality in homes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176:465–472. 2. Chung A, Chang DP, Kleeman MJ, Perry KD, Cahill TA, Dutcher D, McDougall EM, Stroud K. Comparison of real-time instruments used to monitor airborne particulate matter. J Air Waste Manag Assoc 2001; 51:109–120. 3. Jenkins RA, Ilgner RH, Tomkins BA, Peters DW. Development and application of protocols for the determination of response of real-time particle monitors to common indoor aerosols. J Air Waste Manag Assoc 2004;54:229–241. Assessing the Impact of Targeted Tuberculosis Interventions To the Editor: We read with interest the article by Dr. de Vries and colleagues, which discussed a successful mobile screening intervention for tuberculosis (TB) in the Netherlands, where the yield was the equivalent of 327 TB cases detected per 100,000 evaluations (1). Similar success was achieved in Tarrant County, Texas, where, over a 28-month period, a location-based intervention using a comparable mobile screening approach yielded the equivalent of 775 TB cases detected per 100,000 evaluations (2). The Tarrant County intervention included screening and treatment for latent tuberculosis infection (LTBI). Six hundred and eighty-one persons were identified with LTBI. A total of 487 (71.5%) initiated preventive treatment, and 302 (62.0%) completed treatment successfully. Of the 44 with TB, 41 (93.2%) completed adequate treatment. Patients who did not complete treatment (n 5 3) were all diagnosed clinically (i.e., culture-negative) (see Table 1). These high rates of treatment completion in both persons with LTBI and TB disease may be attributable to the successful partnership of community-based organizations and public health departments in identifying, evaluating, and following high-risk populations (3). As TB case rates decline in industrialized countries, elimination efforts will need to focus on more aggressive and targeted interventions to detect cases sooner and ensure adequate treatment supervision in high-risk populations and settings (e.g., HIVinfected persons, illicit drug users, geographic areas with high concentrations of genotype clusters) (2, 4). TB control programs must assess the impact of control activities to maximize efficiency of limited and declining resources. The use of genotyping in TB control has demonstrable added value, not only to detect clustered Mycobacterium tuberculosis isolates, representing potential ongoing transmission, but also to assess the impact of interventions aimed at reducing transmission (5). Current American Thoracic Society guidelines encourage a major expansion of targeted screening and treatment efforts, yet warn that any expansion must include the intent, and infrastructure, required to follow patients to successful treatment completion (6). Therefore, assessing the impact of targeted screening should also include measurements of treatment compliance. Identifying TB is not sufficient to reduce TB transmission; identification must be complemented with prompt initiation of therapy and aggressive follow-up of patients to ensure successful treatment completion. The use of genotyping to assess the 558 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 177 TABLE 1. TREATMENT OUTCOMES FOR LATENT TUBERCULOSIS INFECTION AND TUBERCULOSIS CASES Cases n (%) Latent tuberculosis infection Identified Treatment initiated Initial regimen Long course† Short course‡ Defaulters Lost to follow-up Refused Transferred to another provider Pregnancy Tuberculosis Identified** Culture positive Clinical case Defaulters Lost to follow-up Completing Median Adequate Treatment Midpoint Therapy, n (%)* Completed Spread 681 487 (71.5) 302 (62.0) 364 123 194 146 26 20 221 (60.7) 81 (65.8) — 0 (—) 0 (—) —x 0.68 0.73 0.14–1.0 0.3–1.0 0.44 — 0.39k 0.03–0.74 — 0.19–0.59k 1 (50.0) 0.92 —{ (53.5) (27.4) (28.5) (21.4) (3.8) (2.9) 2 (0.3) 44 30 (68.2) 14 (31.8) 3 (6.8) 3 (100) 30 (100) 11 (78.5) 0 (—) 0.51 0.25–0.69 * Completed at least 80% of recommended doses. Treatments include: INH daily for a minimum of 6 months. ‡ Treatments include: RIF daily for a minimum of 4 months. RIF/PZA bi-weekly for a minimum of 2 months. x Post-transfer preventive medicine completion rate are unavailable. k Proportion of treatment completed prior to transfer. { Cell contains only one patient completing treatment. ** Includes only those who meet Reported Verified Case of Tuberculosis criteria. † impact of targeted interventions in high-risk populations should be encouraged. These assessments should also include measurements of treatment adherence and clinical outcomes of persons with both LTBI and TB disease. Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. PATRICK K. MOONAN Centers for Disease Control and Prevention Atlanta, Georgia STEPHEN E. WEIS University of North Texas Health Science Center Fort Worth, Texas References 1. de Vries G, van Hest RA, Richardus JH. Impact of mobile radiographic screening on tuberculosis among drug users and homeless persons. Am J Respir Crit Care Med 2007;176:201–207. 2. Moonan PK, Oppong J, Sahbazian B, Singh KP, Sandhu R, Drewyer G, Lafon T, Marruffo M, Quitugua TN, Wallace C, et al. What is the outcome of targeted tuberculosis screening based on universal genotyping and location? Am J Respir Crit Care Med 2006;174:599–604. 3. Reves R. Universal genotyping as a tool for establishing successful partnerships for tuberculosis elimination [editorial]. Am J Respir Crit Care Med 2006;174:491–492. 4. Institute of Medicine. Ending neglect: the elimination of tuberculosis in the United States. Washington, DC: National Academy Press; 2000. 5. McNabb SJ, Kammerer JS, Hickey AC, Braden CR, Shang N, Rosenblum LS, Navin TR. Added epidemiologic value to tuberculosis prevention and control of the investigation of clustered genotypes of Mycobacterium tuberculosis isolates. Am J Epidemiol 2004;160: 589–597. 6. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep 2000;49(RR-6): 1–51. See also Am J Respir Crit Care Med 2000;161:S221–S247. 2008 A New Missense Mutation in the CASR Gene in Familial Interstitial Lung Disease with Hypocalciuric Hypercalcemia and Defective Granulocyte Function To the Editor: In their article, Dr. Yang and colleagues described significant genetic differences between familial and sporadic interstitial pneumonias (1). In addition, genetic variations may be expected between the different forms of familial interstitial lung diseases (ILDs), but these remain largely unknown. In 1985, we described the inherited association of ILD, hypocalciuric hypercalcemia (HH), and defective granulocyte function in 43 members of one family (2). The common lung histologic pattern in the three probands was that of a granulomatous disease with aggregates of conchoid bodies surrounded by multinucleated giant cells (2). Auwerx and colleagues (3) showed also that the abnormalities in the calcium homeostasis were similar to those described by Marx and colleagues in benign familial HH (4). We attributed this association of ILD, HH, and defective granulocyte function (2, 3) to an autosomal, dominant inheritance pattern with a variable penetrance of the different abnormalities. Conventional chromosomal analysis did not show abnormalities. We were recently able to demonstrate that the one still living proband (male, 81929, patient 2 in Reference 2), who now has respiratory compromise with frequent respiratory infections and persisting hypercalcemia (between 11.7 and 12.2 mg/dl), is heterozygote for a missense mutation c.623G.C in exon 4 of the calcium-sensing receptor (CASR) gene, and this substitution predicts the replacement of tryptophan by serine at amino acid position 208 (p.Trp208Ser). Trp208 is located in the extracellular calcium binding domain of the receptor and is phylogenetically very strongly preserved in many species. A mutation at this position is thus likely to be pathogenic. It is conceivable that this substitution hampers the normal function of the receptor. Indeed, although Trp and Ser both are neutral polar amino acids, the substitution may cause a sterical hindrance because Trp is markedly larger than Ser. Our finding was based on PCR amplification and DNA sequence analysis of the six coding exons and part of the flanking introns of the CASR gene, using the primers described in Reference 5. The analysis used detects probably more than 99% of the mutations in the CASR gene. This mutation very likely causes the HH in this familial disorder. The mutation has not been described previously, although numerous other mutations in the CASR gene have been found in benign familial HH and in neonatal hyperparathyroidism (5) (see also www.casrdb.mcgill.ca). The intriguing question remains, however, what the relationship is between this substitution in the CASR gene and the associated ILD and defective granulocyte function. Conflict of Interest Statement: M.D. served on advisory boards of Zambon (until 2005), Intermune (since 2006), and Boehringer Ingelheim (since 2007). W.L. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. W.W. was (co-)investigator for studies of Intermune, Centocor, Actelion, and Boehringer Ingelheim. G.M. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.T. serves as a consultant for Intermune. R.B. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. Acknowledgment: The support of the Broere Charitable Foundation is acknowledged. MAURITS DEMEDTS Katholieke Universiteit Leuven Leuven, Belgium