ceptors (NKp46, NKp30 and NKp44). Eur J Immunol 2003; 33:2410–8. 10. Vankayalapati R, Wizel B, Weis SE, et al. The NKp46 receptor contributes to NK cell lysis of mononuclear phagocytes infected with an intracellular bacterium. J Immunol 2002; 168: 3451–7.
Reprints or correspondence: Dr. Andrea De Maria, Dept. of Internal Medicine, University of Genova, No. 10 Largo R. Benzi, Genova I-16132, Italy (
[email protected]). The Journal of Infectious Diseases 2005; 191:1782–3 2005 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2005/19110-0030$15.00
Reply to De Maria
nicians more-rigorously investigate patients known to be infected with HIV. We appreciate De Maria’s comments— as well as those in the editorial commentary [8] that accompanied our article— about potential mechanisms for the observed rapid increase in TB incidence soon after HIV seroconversion. We do not have data on CD4 cell counts or other surrogates for HIV disease progression for the entire cohort, but CD4 cell counts were obtained from hospitalized patients when clinically indicated: of 62 men who were tested within 2 years of HIV seroconversion, 15 had CD4 cell counts !200 cells/ mL. Although biased, this sample demonstrates that there are some rapid progressors in this cohort. We have also reported early increased mortality in this cohort [9]; however, rates by time since seroconversion are similar to those in cohorts in developed countries [10], suggesting that our cohort does not have an unusually high proportion of rapid progressors. Pam Sonnenberg,1 Judith R. Glynn,1 Jill Murray,2 Peter Godfrey-Faussett,1 Katherine Fielding,1 and Stuart Shearer3 1 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom; 2National Institute for Occupational Health, Department of Health and Department of Community Health, University of the Witwatersrand, and 3Gold Fields Limited, Johannesburg, South Africa
References 1. De Maria A. Early active tuberculosis in gold miners who undergo HIV seroconversion: should it influence general practice [letter]? J Infect Dis 2005; 191:1782–3 (in this issue). 2. Sonnenberg P, Glynn JR, Fielding K, Murray J, Godfrey-Faussett P, Shearer S. How soon after infection with HIV does the risk of tuberculosis start to increase? A retrospective cohort study in South African gold miners. J Infect Dis 2005; 191:150–8. 3. Corbett EL, Churchyard GJ, Clayton TC, et al. HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African miners. AIDS 2000; 14:2759–68. 4. Hnizdo E, Murray J. Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners. Occup Environ Med 1998; 55:496–502. 5. Centers for Disease Control and Prevention.
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To the Editor—In response to De Maria’s letter [1] about our study [2], we agree that gold miners are at extremely high risk for tuberculosis (TB) even when not infected with HIV and that the absolute incidence of TB in gold miners with HIV infection cannot be generalized. We do believe, however, that the relative risks of TB by HIV status and the increase in these relative risks soon after HIV seroconversion are more likely to be related to the biological interactions between TB and HIV infection than to the specific context of our study. Silicosis is unlikely to be associated with HIV infection in gold miners, except via associations with age, and age was adjusted for in our analyses; thus, silicosis is unlikely to confound the association between HIV and TB. Furthermore, evidence from other studies indicates that the relative increase in TB incidence due to HIV infection is the same in miners with and without silicosis [3]. Silica dust exposure, even without radiological changes, increases the risk of TB [4]. Adjusting for radiographic evidence of silicosis may, therefore, be misleading, because only more-advanced cases would be included. There may never be general population data with which our data can be compared. It would be difficult to conduct a study in a setting with a low incidence of TB, because the necessary sample size would be very large. Our data, therefore, provide a rare opportunity to explore the
increase in the risk of TB by time since HIV seroconversion. Our study also has the added advantages that exposure to Mycobacterium tuberculosis and HIV in this population are probably unrelated to each other and that diagnosis of pulmonary TB is unrelated to HIV infection. We are not suggesting that clinicians should modify their clinical approach on the basis of our results, because our data support current good practice. Including TB in the differential diagnosis of a symptomatic HIV-positive patient at any time after seroconversion would be appropriate. Similarly, treatment of latent M. tuberculosis infection in a newly diagnosed HIV-positive patient is already recommended [5]. We are, however, suggesting that planners and modelers may need to modify estimates of the early effect of HIV infection on TB incidence. Public-health interventions that reduce transmission of HIV or that reduce the likelihood of progression from M. tuberculosis infection to TB (such as treatment of latent infection) may yield benefits sooner than has been previously anticipated [6]. Since the onset of the HIV epidemic, increases in both pulmonary and extrapulmonary TB incidence have been noted at the gold mines [7]. Our study assessed only pulmonary TB, for a number of reasons. First, we used a validated algorithm for pulmonary TB that could be standardized across the study period. A similar algorithm was not available for extrapulmonary TB. Second, we chose a specific case definition that was likely to include only cases of TB that were caused by M. tuberculosis infection (94% of our cases were culture confirmed), because including disease due to non-TB mycobacteria (which is common at the mines [7]) might have biased the results. Third, although we feel that the chances of detecting pulmonary TB in HIV-positive and HIV-negative miners are similar—and there is active chest radiographic screening in place at the mines—there may be bias in detection of extrapulmonary TB, because cli-
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Reprints or correspondence: Dr. Pam Sonnenberg, Communicable Disease Surveillance Centre, 61 Colindale Ave., London NW9 5EQ, United Kingdom (
[email protected]). The Journal of Infectious Diseases 2005; 191:1783–4 2005 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2005/19110-0031$15.00
1784 • JID 2005:191 (15 May) • CORRESPONDENCE
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Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. MMWR Recomm Rep 1998; 47(RR-20):1–58. Currie CS, Williams BG, Cheng RC, Dye C. Tuberculosis epidemics driven by HIV: is prevention better than cure? AIDS 2003; 17:2501–8. Churchyard GJ, Kleinschmidt I, Corbett EL, Mulder D, De Cock KM. Mycobacterial disease in South African gold miners in the era of HIV infection. Int J Tuberc Lung Dis 1999; 3:791–8. Srikantiah P, Charlebois E, Havlir DV. Rapid increase in tuberculosis incidence soon after infection with HIV—a new twist in the twin epidemics. J Infect Dis 2005; 191:147–9. Glynn JR, Sonnenberg P, Nelson G, Bester A, Shearer S, Murray J. The effect of HIV on all cause mortality during employment in a large cohort of South African gold miners with known dates of seroconversion and 10 years of follow-up [abstract MoPeC3371]. XV International AIDS Conference (Bangkok, Thailand). MedGenMed 2004; 6:MoPeC3371 [eJIAS 2004; 1:MoPeC3371]. Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis. Lancet 2000; 355:1131–7.
