Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis.

Chromosome 5q31 spans the T helper (Th) 2-related cytokine gene cluster, which is potentially important in Th1/Th2 immune responses. The chromosome 5q23.2-31.3 has been recently identified as a region with suggestive evidence of linkage to tuberculosis in the Asian population. With the aim of fine-mapping a putative tuberculosis susceptibility locus, we investigated a family-based association test between the dense single nucleotide polymorphism (SNP) markers within chromosome 5q31 and tuberculosis in 205 Thai trio families. Of these, 75 SNPs located within candidate genes covering SLC22A4, SLC22A5, IRF1, IL5, RAD50, IL13, IL4, KIF3A and SEPT8 were genotyped using the DigiTag2 assay. Association analysis revealed the most significant association with tuberculosis in haplotypes comprising SNPs rs274559, rs274554 and rs274553 of SLC22A5 gene (P(Global)=2.02 x 10(-6)), which remained significant after multiple testing correction. In addition, two haplotypes within the SLC22A4 and KIF3A region were associated with tuberculosis. Haplotypes of SLC22A5 were significantly associated with the expression levels of RAD50 and IL13. The results show that the variants carried by the haplotypes of SLC22A4, SLC22A5 and KIF3A region potentially contribute to tuberculosis susceptibility among the Thai population.

Genome-wide SNP-based linkage analysis of tuberculosis in Thais.

Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide. Human protective immunity that contains tuberculosis after infection has not been clearly defined. To gain insight into host genetic factors, nonparametric linkage analysis was performed using high-throughput microarray-based single nucleotide polymorphism (SNP) genotyping platform, a GeneChip array comprised 59 860 bi-allelic markers, in 93 Thai families with multiple siblings, 195 individuals affected with tuberculosis. Genotyping revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis (Z(lr) statistics=3.01, logarithm of odds (LOD) score=2.29, empirical P-value=0.0005), and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate (maximum LOD score=2.57 and 3.33, permutation P-value=0.0187 and 0.0183, respectively). These results imply a new evidence of genetic risk factors for tuberculosis in the Asian population. The significance of these ordered subset results supports a clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients. The linkage information from a specific ethnicity may provide unique candidate regions for the identification of the susceptibility genes and further help elucidate the immunopathogenesis of tuberculosis.

Directly observed treatment is associated with reduced default among foreign tuberculosis patients in Thailand.

SETTING: Thailand's Tuberculosis (TB) Active Surveillance Network in four provinces in Thailand. OBJECTIVE: As treatment default is common in mobile and foreign populations, we evaluated risk factors for default among non-Thai TB patients in Thailand. DESIGN: Observational cohort study using TB program data. Analysis was restricted to patients with an outcome categorized as cured, completed, failure or default. We used multivariate analysis to identify factors associated with default, including propensity score analysis, to adjust for factors associated with receiving directly observed treatment (DOT). RESULTS: During October 2004-September 2006, we recorded data for 14359 TB patients, of whom 995 (7%) were non-Thais. Of the 791 patients analyzed, 313 (40%) defaulted. In multivariate analysis, age>or=45 years (RR 1.47, 95%CI 1.25-1.74), mobility (RR 2.36, 95%CI 1.77-3.14) and lack of DOT (RR 2.29, 95%CI 1.45-3.61) were found to be significantly associated with default among non-Thais. When controlling for propensity to be assigned DOT, the risk of default remained increased in those not assigned DOT (RR 1.99, 95%CI 1.03-3.85). CONCLUSION: In non-Thai TB patients, DOT was the only modifiable factor associated with default. Using DOT may help improve TB treatment outcomes in non-Thai TB patients.

Tuberculosis services and treatment outcomes in private and public health care facilities in Thailand, 2004-2006.

BACKGROUND: The World Health Organization recommends that national tuberculosis (TB) programs encourage public and private providers to follow the 'International standards for tuberculosis care'. We assessed services and treatment outcomes in TB patients in public and private facilities to inform public-private mix scale-up in Thailand. METHODS: We prospectively collected data on TB patients in four provinces and the national infectious diseases hospital during 2004-2006. We analyzed services and outcomes among new pulmonary TB patients according to facility type. RESULTS: Of 7526 patients, 4539 (60%) were treated in small public facilities, 2275 (30%) in large public facilities and 712 (10%) in private facilities. Compared with the private sector, more public sector patients had at least two sputum smears examined, were prescribed a standard anti-tuberculosis regimen and received directly observed therapy; however, public sector facilities also performed suboptimally. Treatment outcomes were unsuccessful for 237 (33%) patients in private facilities, and for respectively 1018 (23%) and 655 (29%) patients in small and large public facilities. CONCLUSIONS: TB diagnostic and treatment services and outcomes should be enhanced in both public and private facilities in Thailand. Initiatives are needed to improve treatment outcomes and increase the use of microscopy, standardized TB regimens, and directly observed therapy in the public and private sectors.

Informed patient consent for defaulter tracing: should we obtain it?

Active default tracing is an integral part of tuberculosis (TB) programmatic control. It can be differentiated into the tracing of defaulters (patients not seen at the clinic for > or =2 months) and 'late patients' (late for their scheduled appointments). Tracing is carried out to obtain reliable information about who has truly died, transferred out or stopped treatment, and, if possible, to persuade those who have stopped treatment to resume. This is important because, unlike routine care for non-communicable diseases, TB has the potential for transmission to other members of the community, and therefore presents the issue of the rights of the individual over the rights of the community. For this reason, default or 'late patient' tracing (defined together as default tracing in this article) has been incorporated into standard practice in most TB programmes and, in many industrialised countries, it is also a part of public health legislation. In resource-poor countries with limited access to phones or e-mails, default tracing involves active home visits. In this Unresolved Issues article, we discuss the need for patient consent within both the programmatic and the research context; we describe how this subject arose during operational research training at the Research Institute of Tuberculosis in Japan; we provide comments from individuals who are experienced and skilled at international and national TB control; and finally we offer some conclusions about the way forward. This is not an easy subject, and we welcome open debate on the issue.

Tuberculosis preventative therapy as part of a care package for people living with HIV in a district of Thailand.

We studied the risk factors for default in isoniazid preventative therapy (IPT) against tuberculosis in 412 people living with HIV (PLWH) in Mae Chan Hospital, Thailand. Default rates decreased from 57% in 1995 to 17% in 1999. Female sex, residence inside Mae Chan District, and registered in the PLWH group at enrollment of IPT were associated with lower default rates. The integration of IPT into the PLWH day care centre activities over the years might contribute to improvements.

Barriers to human immunodeficiency virus testing of tuberculosis patients in Thailand, 2004-2007.

SETTING: Tuberculosis (TB) clinics in five provinces and one national referral hospital in Thailand. OBJECTIVE: To identify risk factors for TB patients not receiving human immunodeficiency virus (HIV) pre-test counseling and testing in Thailand. DESIGN: We collected data on TB patients treated at participating facilities from 2004 to 2007. Patients with known HIV status at the time of TB diagnosis were excluded from the analysis. We performed multivariate logistic regression to determine patient and facility characteristics associated with HIV counseling and testing. RESULTS: Of 15 903 TB patients, HIV pre-test counseling was provided to 13 604 (86%). HIV testing was provided to 11 702 (86%) of those counseled. Of 6141 patients with unknown HIV status, 2323 (38%) were treated in facilities that provide HIV testing in TB clinics compared with 6412 (58%) of 11 003 non-HIV-infected and 3814 (62%) of 6121 HIV-infected patients (P < 0.05). In multivariate analysis, patients treated in facilities in which HIV testing of TB patients was performed somewhere other than the TB clinic were significantly less likely to undergo HIV pre-test counseling (adjusted OR 1.55, 95%CI 1.28-1.86). CONCLUSION: In Thailand, providing HIV testing directly in TB clinics, rather than in other settings, may increase the proportion of TB patients with known HIV status.