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Zhang F.-R.,Shandong Provincial Institute of Dermatology and Venereology | Liu H.,Shandong Provincial Institute of Dermatology and Venereology | Irwanto A.,Genome Institute of Singapore | Irwanto A.,National University of Singapore | And 68 more authors.
New England Journal of Medicine

BACKGROUND: Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome. METHODS: We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls. RESULTS: Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P = 3.84×10-13). HLAB*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P = 6.84×10-25). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans. CONCLUSIONS: HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. Copyright © 2013 Massachusetts Medical Society. Source

Cheng S.,National Center for Tuberculosis Control and Prevention | Chen W.,National Center for Tuberculosis Control and Prevention | Yang Y.,Shenzhen Chronic Disease Control Center | Chu P.,Capital Medical University | And 11 more authors.

Introduction:To understand better the risk of tuberculosis transmission with increasing delay in tuberculosis treatment, we undertook a retrospective cohort study in Shenzhen, China.Methods:All pulmonary tuberculosis cases in the Shenzhen tuberculosis surveillance database from 1993-2010 were included. Sputum smear positivity and presence of pulmonary cavity were used as proxies for risk of tuberculosis transmission.Results:Among 48,441pulmonary tuberculosis cases, 70% presented with symptoms of pulmonary TB, 62% were sputum smear positive, and 21% had a pulmonary cavity on chest x-ray. 95.3% of patients self-presented for evaluation of illness after a median 58 days of delay after symptoms began. The proportion presenting sputum smear positive (p<0.001) and with a pulmonary cavity (p<0.001) increased significantly with increasing duration of delay.Conclusions:Delayed diagnosis and treatment of tuberculosis is associated with a significantly increased risk of pulmonary sputum smear positivity and pulmonary cavity. To decrease risk of transmission, treatment delay needs to be reduced further. © 2013 Cheng et al. Source

Mo Y.-S.,Shenzhen Chronic Disease Control Center | Pan P.,Shenzhen Chronic Disease Control Center | Wang L.-Y.,Shenzhen Chronic Disease Control Center | Yang Y.-Z.,Shenzhen Chronic Disease Control Center
Journal of Clinical Dermatology

A 41-year-old man has been diagnosed as lupus vulgaris. Perianal erythema and ulcers have lasted for about 2 years while he began to have pulmonary tuberculosis 5 years ago. Histopathological detection of lesion showed that tuberculous tubercle presented in shallow dermis. Lowenstein-Jensen culture with tissue fluid from lesion was positive for bacillus tubercu-losis typus humanus, Regular anti-TB treatment was not effective, which is identified as multidrug-resistant (MDR), including isoniazid, rifampicin, ethambutol and rifapentine. Source

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