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Background: The epidemic of Human Immunodeficiency Virus (HIV) infection led blood banks to initiate donation deferral criteria based on self-reported risk factors. However little information is available on the differences in reporting risk factors before and after HIV status is known.Methods: Between April and July 1994, blood donors in a provincial hospital in northern. Thailand were interviewed at the time of donation, about their demographic characteristics and risk factors. All donors had agreed to learn their test results and were called back for post-test counselling and reinterview.Results: HIV-positive blood donors were more likely to change from 'denying' to 'acknowledging' risk factors while HIV-negatives were more likely to change from 'acknowledging' to 'denying'. The differences between risk factors obtained before and after test results were known resulted in stronger, weaker or even opposite risk measures.Conclusion: The study results raise questions about the impact of the differences in reporting HIV-related risk factors by the donors on how effective donation deferral criteria can be developed. [ABSTRACT FROM AUTHOR]

To determine contributions of previously incarcerated persons to tuberculosis (TB) transmission in the community, we performed a healthcare facility-based cohort study of TB patients in Thailand during 2017-2020. We used whole-genome sequencing of Mycobacterium tuberculosis isolates from patients to identify genotypic clusters and assess the association between previous incarceration and TB transmission in the community. We identified 4 large genotype clusters (>10 TB patients/cluster); 28% (14/50) of the patients in those clusters were formerly incarcerated. Formerly incarcerated TB patients were more likely than nonincarcerated patients to be included in large clusters. TB patients within the large genotype clusters were geographically dispersed throughout Chiang Rai Province. Community TB transmission in the community was associated with the presence of formerly incarcerated individuals in Thailand. To reduce the risk for prison-to-community transmission, we recommend TB screening at the time of entry and exit from prisons and follow-up screening in the community.

Whole-genome sequencing (WGS) analysis has great discriminative power for detecting similar molecular fingerprints of suspected tuberculosis (TB) clusters. The proportion of TB cases within clusters and the associated risk factors are important epidemiological parameters guiding appropriate outbreak control strategies in endemic settings. We conducted a hospital-based TB case-cohort study between 2003 and 2011 in the northernmost province of Thailand. We identified TB clusters by Mycobacterium tuberculosis WGS and analysed the risks of TB clustering and the characteristics of large clusters compared with small clusters. Among 1146 TB isolates, we identified 77 clusters with 251 isolates defined by a 5-single-nucleotide variant (SNV) cutoff and 112 clusters with 431 isolates defined by a 12-SNV cutoff. Twelve large clusters with 6 isolates or more in each cluster were identified by a 12-SNV cutoff. Sublineage 2.2.1 (both Ancestral and Modern) strains and imprisonment were independently associated with large clusters. Furthermore, although large clusters of Lineage 2.2.1/Ancestral strains included a high number of prisoners, Lineage 2.2.1/Modern strain clusters were only associated with treatment failures and drug resistance. Heterogeneity among lineage strains was observed with respect to large-cluster characteristics. Patients with an increased TB-transmission tendency should be priority targets for contact investigations and outbreak interventions to prevent ongoing transmission., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The current Thai guideline recommends that among people living with HIV, isoniazid preventive therapy (IPT) should be given to those with a positive tuberculin skin test (TST). We conducted a case-control study, nested within a cohort study, in Chiang Rai Province in Thailand to determine the role of TST in predicting the development of active tuberculosis (TB) within the following 2 years. Comparison between participants with CD4+ counts <50cells/mm 3 to those with CD4+ ≥200cells/mm 3 revealed that TST results were less sensitive (7.7% vs 50.0%) and had a lower negative predictive value (73.1% vs 97.3%) in those with a CD4+ count <50cells/mm 3 . In people with HIV, using a positive TST result as a criterion for initiating IPT inadvertently decreases the benefits of IPT, especially among those with low CD4+ counts., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

SETTING: This study was conducted among tuberculosis (TB) patients in a highly endemic Thai province. OBJECTIVE: To evaluate the association between different Mycobacterium tuberculosis lineages and clinical characteristics, especially mortality. DESIGN: We enrolled 1,304 TB patients registered from 2002-2011 with culture isolates whose lineages were identified by specific regions of deletion. Data on mortality within 1 year of follow-up were extracted from the registration system and hospital records. Mortality-associated risk factors, including bacterial lineages, as independent variables were analysed using Cox regression models. RESULTS: Of 1,304 isolates, 521 (40.0%) and 582 (44.6%) belonged to Indo-Oceanic and East-Asian lineages, respectively. Indo-Oceanic strains significantly increased the mortality risk compared with East-Asian strains (adjusted hazard ratio [aHR] 1.42, 95%CI 1.02-1.99) or modern lineages (aHR 1.49, 95%CI 1.08-2.06) in the 172 patients who died within 1 year after TB diagnosis. The former also caused significantly higher mortality than modern lineages among patients who died within 6 months after TB diagnosis (aHR 1.62, 95%CI 1.12-2.35). No significant association was found between drug resistance and death. CONCLUSION: In Thailand, the Indo-Oceanic lineage of M. tuberculosis increased mortality risk compared with modern lineages or the East-Asian lineage, the latter being considered highly virulent in previous studies.

Background: The neutrophil to lymphocyte ratio (NL ratio) has been reported to be a predictive biomarker of tuberculosis (TB). We assessed the association between the NL ratio and the incidence of active TB cases within 1 year after TB screening among HIV-infected individuals in Thailand., Methods: A day care center that supports HIV-infected individuals in northernmost Thailand performed TB screening and follow-up visits. We compared the baseline characteristics between the TB screening positive group and the TB screening negative group. The threshold value of NL ratio was determined by cubic-spline curves and NL ratios were categorized as high or low NL ratio. We assessed the association between NL ratio and progression to active TB within 1-year using the Cox-proportional hazard model., Results: Of the 1064 HIV-infected individuals who screened negative for TB at baseline, 5.6% (N = 60) eventually developed TB and 26 died after TB diagnosis. A high NL ratio was associated with a higher risk of TB (adjusted hazard ratio (aHR) 2.19, 95% CI: 1.23-3.90), after adjusting for age, sex, ethnicity, CD4 counts, and other risk factors. A high NL ratio in HIV-infected individuals with normal chest X-ray predicted TB development risk. In particular, a high NL ratio with TB symptoms could predict the highest risk of TB development (aHR 2.58, 95%CI: 1.07-6.23)., Conclusions: Our results showed that high NL ratio increased the risk of TB. NL ratio combined with TB symptoms could increase the accuracy of TB screening among HIV-infected individuals.

Antituberculosis drug-induced liver injury (ATDILI) is a common side effect leading to tuberculosis (TB) treatment disruption. The mechanism of the disease remains poorly understood. We conducted a genomewide association study (GWAS) to investigate all possible genetic factors of ATDILI in Thai patients. This study was carried out in Thai TB patients, including 79 ATDILI cases and 239 tolerant controls from our network hospitals in Thailand. Nearly 1 million single-nucleotide polymorphisms (SNPs) were genotyped across the whole genome using an Illumina OmniExpress Exome BeadChip array. In the discovery stage, we identified strong association signals on chromosome 8 originating from the N -acetyltransferase ( NAT2 ) region. The A allele of rs1495741, the top SNP in the intergenic region of NAT2 and PSD3 (14 kb from NAT2 ), was significantly associated with ATDILI (recessive model, odds ratio of 6.01 [95% confidence interval, 3.42 to 10.57]; P  = 6.86E-11). This particular SNP was reported as a tag SNP for NAT2 inferred phenotypes. The AA, AG, and GG genotypes represented NAT2 slow acetylators, intermediate acetylators, and fast acetylators, respectively. The tag SNP genotypes demonstrated a concordance rate of 94.98% with NAT2 acetylator phenotypes. This GWAS shows that NAT2 is the most important risk factor for ATDILI in the Thai population., (Copyright © 2019 American Society for Microbiology.)

Tuberculosis presents a global health challenge. Mycobacterium tuberculosis is divided into several lineages, each with a different geographical distribution. M. tuberculosis lineage 1 (L1) is common in the high-burden areas in East Africa and Southeast Asia. Although the founder effect contributes significantly to the phylogeographic profile, co-evolution between the host and M. tuberculosis may also play a role. Here, we reported the genomic analysis of 480 L1 isolates from patients in northern Thailand. The studied bacterial population was genetically diverse, allowing the identification of a total of 18 sublineages distributed into three major clades. The majority of isolates belonged to L1.1 followed by L1.2.1 and L1.2.2. Comparison of the single nucleotide variant (SNV) phylogenetic tree and the clades defined by spoligotyping revealed some monophyletic clades representing EAI2&#95;MNL, EAI2&#95;NTM and EAI6&#95;BGD1 spoligotypes. Our work demonstrates that ambiguity in spoligotype assignment could be partially resolved if the entire DR region is investigated. Using the information to map L1 diversity across Southeast Asia highlighted differences in the dominant strain-types in each individual country, despite extensive interactions between populations over time. This finding supported the hypothesis that there is co-evolution between the bacteria and the host, and have implications for tuberculosis disease control.

This study examined the genetic diversity and dynamicity of circulating Mycobacterium tuberculosis strains in Thailand using nearly neutral molecular markers. The single nucleotide polymorphism (SNP)-based genotypes of 1,414 culture-positive M. tuberculosis isolates from 1,282 pulmonary tuberculosis (PTB) and 132 extrapulmonary TB (EPTB) patients collected from 1995 to 2011 were characterized. Among the eight SNP cluster groups (SCG), SCG2 (44.1%), which included the Beijing (BJ) genotype, and SCG1 (39.4%), an East African Indian genotype, were dominant. Comparisons between the genotypes of M. tuberculosis isolates causing PTB and EPTB in HIV-negative cases revealed similar prevalence trends although genetic diversity was higher in the PTB patients. The identification of 10 reported sequence types (STs) and three novel STs was hypothesized to indicate preferential expansion of the SCG2 genotype, especially the modern BJ ST10 (15.6%) and ancestral BJ ST19 (13.1%). An association between SCG2 and SCG1 genotypes and particular patient age groups implies the existence of different genetic advantages among the bacterial populations. The results revealed that increasing numbers of young patients were infected with M. tuberculosis SCGs 2 and 5, which contrasts with the reduction of the SCG1 genotype. Our results indicate the selection and dissemination of potent M. tuberculosis genotypes in this population. The determination of heterogeneity and dynamic population changes of circulating M. tuberculosis strains in countries using the Mycobacterium bovis BCG (bacillus Calmette-Guérin) vaccine are beneficial for vaccine development and control strategies., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The emergence of drug resistant Mycobacterium tuberculosis has become a global threat to tuberculosis (TB) prevention and control efforts. This study aimed to determine the drug resistance profiles and DNA fingerprints of M. tuberculosis strains isolated from patients with relapsed or retreatment pulmonary TB in Chiang Rai province in northern Thailand. Significant differences in multidrug resistance (MDR) (P = 0.025) and resistance to isoniazid (P = 0.025) and rifampin (P = 0.046) between first and second registrations of patients with retreatment TB were found. However, there were no significant differences in resistance to any drugs in patients with relapsed TB. The rate of MDR-TB strains was 12.2% among new patients at first registration, 22.5% among patients with recurrence who had previously undergone treatment at second registration and 12.5% at third registration. Two retreatment patients whose initial treatment had failed had developed MDR-TB with resistance to all TB drugs tested, including rifampin, isoniazid, streptomycin and ethambutol. IS6110-RFLP analysis revealed that 66.7% (10/15 isolates) of MDR-TB belonged to the Beijing family. In most cases, IS6110-RFLP patterns of isolates from the same patients were identical in relapse and retreatment groups. However, some pairs of isolates from retreatment patients after treatment failure had non-identical IS6110-RFLP patterns. These results suggest that, after failure and default treatment, patients with retreatment tuberculosis have a significantly greater risk of MDR-TB, isoniazid and rifampin resistance than do other patients., (© 2012 The Societies and Wiley Publishing Asia Pty Ltd.)

Tuberculosis (TB) is one of the most devastating chronic infectious diseases, but the role of host genetics in disease development after infection in this disease remains unidentified. Genome-wide association studies (GWASs) in Thais and Japanese were carried out and separately analyzed, attempted replication, then, combined by meta-analysis were not yielding any convincing association evidences; these results suggested that moderate to high effect-size genetic risks are not existed for TB per se. Because of failure in replication attempt of the top 50 single-nucleotide polymorphisms (SNPs) identified form meta-analysis data, we empirically split TB cases into young TB case/control data sets (GWAS-T(young)=137/295 and GWAS-J(young)=60/249) and old TB case/control data sets (GWAS-T(old)=300/295 and GWAS-J(old)=123/685), re-analyzed GWAS based on age-stratified data and replicated the significant findings in two independent replication samples (young TB; Rep-T(young)=155/249, Rep-J(young)=41/462 and old TB; Rep-T(old)=212/187, Rep-J(old)=71/619). GWAS and replication studies conducted in young TB identified at-risk locus in 20q12. Although the locus is located in inter-genic region, the nearest genes (HSPEP1-MAFB) from this locus are promising candidates for TB susceptibility. This locus was also associated with anti-TNF responsiveness, drug with increased susceptibility for TB. Moreover, eight SNPs in an old TB meta-analysis and six SNPs in young TB meta-analysis provided replication evidences but did not survive genome-wide significance.These findings suggest that host genetic risks for TB are affected by age at onset of TB, and this approach may accelerate the identification of the major host factors that affect TB in human populations.

Granulysin and interferon-gamma (IFN-γ) have broad antimicrobial activity which controls Mycobacterium tuberculosis (M. tuberculosis) infection. Circulating granulysin and IFN-γ concentrations were measured and correlated with clinical disease in Thai patients with newly diagnosed, relapsed and chronic tuberculosis (TB). Compared to controls, patients with newly diagnosed, relapsed and chronic TB had lower circulating granulysin concentrations, these differences being significant only in newly diagnosed and relapsed TB (P < 0.001 and 0.004, respectively). Granulysin concentrations in patients with newly diagnosed and relapsed TB were significantly lower than in those with chronic TB (P= 0.003 and P= 0.022, respectively). In contrast, significantly higher circulating IFN-γ concentrations were found in patients with newly diagnosed and relapsed TB compared to controls (P < 0.001). The IFN-γ concentrations in newly diagnosed and relapsed patients were not significantly different from those of patients with chronic TB. However, in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from patients with newly diagnosed, relapsed and chronic TB with purified protein derivative (PPD) or heat killed M. tuberculosis (H37Ra) enhanced production of granulysin by PBMCs. In vitro, stimulation of PBMCs of newly diagnosed TB patients with PPD produced greater amounts of IFN-γ than did controls, while those stimulated with H37Ra did not. The results demonstrate that patients with active pulmonary TB have low circulating granulysin but high IFN-γ concentrations, suggesting possible roles in host defense against M. tuberculosis for these agents., (© 2011 The Societies and Blackwell Publishing Asia Pty Ltd.)

The T helper type 1 (Th1) immune response plays an important role in protective immunity, pathophysiology and development of tuberculosis (TB). To investigate whether osteopontin (OPN) and other Th1 response-related molecules are associated withTB disease status, including co-infection with HIV, and response to anti-TB treatment, circulating levels of full-length OPN (F-OPN), thrombin-cleaved N-terminal fragment of OPN (N-half OPN), IFN-gamma, IP-10, IL-18, IL-12/ IL-23 (p40), IL-10, IL-15 and C-reactive protein (CRP) were measured before and after anti-TB treatment. Patients with newly active pulmonary TB had significantly higher plasma levels of F-OPN, IFN-gamma and CRP than healthy controls (HC). F-OPN, N-half OPN, IFN-gamma, IP-10, IL-18 and IL-10 levels were higher in patients with extensive TB/HIV co-infection than in patients with a single disease of TB or HIV. Plasma levels of F-OPN correlated well with those of IP-10, IL-18 and N-half OPN among patients with active TB. The F-OPN, IFN-gamma, IP-10 and CRP levels decreased significantly after effective anti-TB treatment. These data suggest that circulating OPN and Th1 response-related molecules, including IFN-gamma, may be regulated in response to expansion of active TB and could serve as markers of disease activity before and during treatment.

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.

Spoligotyping and variable-number tandem repeats (VNTR) typing have been increasingly used for differentiating Mycobacterium tuberculosis strains with low copy numbers of IS6110. However, there are few studies comparing their potential to type the strains originating from South and Southeast Asia where many of the isolates have only a few copies, or even single copy, of IS6110. Here, we evaluated the genotyping of 187M. tuberculosis isolates harboring 1-6 copies of IS6110, available from a population-based study in Chiangrai, northern Thailand during 1998-2000, using spoligotyping and VNTR typing. The low-copy-number isolates constituted about 34% of all M. tuberculosis isolated in the province. Discriminating capacities and cluster identification by the two methods were compared with each other and to those obtained by the standard IS6110-restriction fragment length polymorphism (RFLP) method. We found that VNTR typing based on the studied 10-loci set generated more distinct patterns (151 patterns) than spoligotyping (54 patterns) and IS6110-RFLP (65 patterns). Most of the RFLP- or spoligotyping-defined clusters were subdivided by VNTR typing. Combining IS6110-RFLP with VNTR typing produced 164 distinct patterns and 21.9% of clustered isolates whereas the combination of IS6110-RFLP and spoligotyping gave 103 different patterns and 59.4% of clustered isolates. Our results confirm the utility of VNTR typing as the secondary method of choice for investigating the epidemiology of M. tuberculosis with low copy numbers of IS6110.

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.

The low birth weight (LBW) infant has a much higher risk of mortality and morbidity in infancy and early childhood. This study examined the effects of maternal HIV infection and other risk factors for LBW (< 2,500 g). A retrospective study of mothers who delivered at Mae Chan Hospital from 1997 to 2002 was conducted. Logistic regression was used to adjust for confounding factors. There were 266 infants born to HIV-seropositive mothers and 5,872 infants born to HIV-negative mothers. Low birth weight was significantly associated with maternal HIV status, gestational age, antenatal care, maternal age less than 20 years, and > 35 years. Maternal HIV positive status, young maternal age and gestational age were significant factors after adjusting for potential confounders. No significant effect of hilltribe on LBW was found. The results underline the need for nutritional surveillance and dietary counseling. HIV-seropositive women must receive early and continuing antenatal care for good pregnancy outcomes.

Background: We aim here to determine the appropriate dose of nevirapine (NVP) in Thai HIV-tuberculosis (TB)-coinfected patients receiving rifampicin., Methods: Thirty-two HIV-infected adults with CD4+ T-cell counts <200 cells/mm3 and active TB, receiving rifampicin for 2-6 weeks were randomized to receive either NVP 400 mg (NVP400) or 600 mg (NVP600) per day plus two nucleoside reverse transcriptase inhibitors; a 2-week NVP lead-in was performed at 200 mg once daily (OD) and 200 mg twice daily, respectively. Plasma NVP levels were determined at weeks 2, 4 and 12. Twelve-hour pharmacokinetics (PK) were obtained (n=20) at week 4., Results: Baseline body weight was comparable. There were more patients with NVP plasma concentration at 12 h (C12) <3.1 mg/l at week 2 in NVP400 than in NVP600 (79% versus 19%, respectively; P=0.002). However, the proportions were comparable at weeks 4 and 12. From week 4, 12 h PK studies showed that NVP400 had lower median NVP area under the plasma concentration-0-12 h (AUC0-12 h, maximum concentration in plasma (Cmax) and C12 than NVP600 (P<0.05). Four patients in NVP600 developed NVP hypersensitivity. At week 48, the median CD4+ T-cell count rise and proportion with viral load <50 copies/ml (intention-to-treat analysis 56% versus 50% and as-treated analysis 75% versus 89%) were comparable., Conclusions: In rifampicin-treated patients, 200 mg NVP OD lead-in led to a significant short-term suboptimal NVP C12 level, while NVP 400 mg lead-in then 600 mg/day was associated with a high rate of NVP hypersensitivity. Forty-eight week efficacy was comparable. Thus, NVP 600 mg/day in rifampicin-treated patients is not recommended.

A cross-sectional survey of 271 day care center (DCC) members at 9 district hospitals was undertaken using an interviewer-administered questionnaire to assess the psychosocial and economic impact of the services provided by DCCs to people living with HIV/AIDS (PLWHA) and the costs of attending DCCs in Chiang Rai Province in Thailand. Data on the socioeconomic and demographic background of the participants, their reasons for attending DCCs, their medical services usage, the changes DCCs made on their lives, and the cost of attending DCCs were collected. "Receiving information" (37%) and "meeting friends" (32%) were the two most common reasons while fewer participants gave "physical examination" (6%) and "counseling" (0.4%) as their reasons for attending DCCs. Nearly half became more positive about their lives and 40% learned how to live with the disease. Through DCCs, 24% and 58% were receiving prophylaxis for tuberculosis and Pneumocystis carinii pneumonia respectively, and 15% were taking antiretrovirals. The majority (85%) lived with 30 minutes of DCCs, and incurred travel cost up to 30 Baht (1 USD approximately 40 Baht). The mean monthly income of those with jobs was 1,565 Baht and 42% lost wages when attending DCCs, more than half of whom were the main income earners in their families. In conclusion, DCCs benefit PLWHA through their educational and psychological support. However, they can be further utilized for their medical services. As an expansion of antiretroviral treatment is planned in Thailand, the DCCs' role should be fully explored and clearly defined. Minimizing economic and geographical barriers to access are some of the most immediate challenges.

A molecular epidemiological study of the gag p17 and env-V3 regions on HIV-infected drug users and blood donors was carried out in northern Thailand from 1998 through 2002 to determine the predominant subtype and consensus sequence (CS) for circulating HIV-1 strains. CRF01&#95;AE was concluded to be a predominant strain and the nucleotide CSs in gag p17 and env-V3 showed only 1.26% and no difference from CS in the Los Alamos database, respectively. Our env-V3 CS was identical to the previously published CSs, suggesting that the CS was very conserved from 1990 through 2002 in Thailand. Gag p17 and env-V3 nucleotide sequences of seroconvertors in our subjects were quite similar to the CS and conserved for at least 9 and 6 years postinfection, respectively. These results suggest that the CS approach to the HIV-1 antigen design could overcome HIV diversity and help us develop an effective HIV/AIDS vaccine.

Setting: Chiang Rai province, Northern Thailand., Objective: To study the probability of acquiring drug resistance to isoniazid (H) and rifampicin (R) on recurrence after treatment success, default and failure, among sputum smear-positive pulmonary tuberculosis (TB) patients treated with standardised short-course chemotherapy., Design: Retrospective analysis of registration records of TB patients from May 1996 to December 2000 in Chiang Rai, where routine drug susceptibility testing (DST) is conducted for surveillance purposes. Patients registered twice or more were examined., Results: Of 59 cases treated with HRZE/HR who underwent DST at the time of registration, 31 were fully susceptible to H and R at first registration, of whom four acquired drug resistance to H or R. Of 13 cases resistant to H or R at first registration, 11 became multidrug-resistant (MDR). The remaining 15 patients were original MDR cases. Among 28 MDR or H- or R-resistant cases, six reverted from resistant to susceptible., Discussion: A high proportion of patients with H- or R-resistant TB became MDR after treatment with 2HRZE/HR. Using this regimen, MDR may increase in a population with a high prevalence of H or R resistance. We are unable to explain why some drug-resistant cases became drug-susceptible. Further investigation is necessary.

Setting: Combined hospital-based and home visit, Chiang Rai, Thailand., Objective: To describe the results of screening of tuberculosis (TB) and HIV infection among household contacts of TB patients in an area endemic for HIV., Design: Consecutive new smear-positive TB patients were interviewed and their household contacts were screened for TB including tuberculin skin test (TST), chest radiography, and sputum examination. Voluntary HIV testing and counseling was also performed., Results: Of 499 pulmonary TB index cases, 197 (39.5%) were HIV-positive; 1200 household contacts were screened for TB and 890 (74.2%) agreed to HIV testing. The prevalence of TST induration > or = 10 mm and active TB among household contacts of HIV-positive pulmonary TB cases were 46.2% (225/487) and 2.9% (14/490), and among household contacts of HIV-negative TB cases were 62.1% (438/705) and 4.4% (31/710), respectively. Higher HIV prevalence was found among contacts of HIV-positive TB patients than among household contacts of HIV-negative TB index cases (52/376, 13.8% vs. 13/514, 2.5%) (P < 0.001). Spouses of HIV-positive TB cases had the highest HIV prevalence (36/74, 48.6%). Among the household contacts who were HIV-positive, 9.5% (7/74) had active TB., Conclusion: Integrated counseling and screening for TB and HIV should be provided for household contacts of TB patients in an HIV endemic area.

Setting: A provincial referral hospital in northern Thailand, where a cross-sectional study during 1995-1996 reported on the occupational risk of Mycobacterium tuberculosis transmission., Objective: To describe the effectiveness of prevention strategies for nosocomial tuberculosis (TB)., Design: A prospective study among health care workers (HCW) including annual tuberculin skin test (TST) screening and active TB surveillance. Following a comprehensive risk assessment, preventive interventions were implemented targeting HCWs, hospitalised patients, and the hospital environment., Results: The number of pulmonary TB cases diagnosed increased steadily from 102 in 1990 to 356 in 1999. The TST conversion rate was 9.3 (95% CI 3.3-15) per 100 person-years (py) in 1995-1997, but declined steadily to 2.2 (95% CI 0.0-5.1) in 1999. HCWs first screened within 12 months of employment had higher TST conversion rates (adjusted RR = 9.5, 95% CI 1.8-49.5) compared to those employed for longer than 12 months. The annual rate of active TB per 100 000 HCWs was 536 in 1995-1999., Conclusion: These HCWs were exposed to active TB patients and were at risk for M. tuberculosis infection, particularly during their first 12 months of employment. Implementation of nosocomial TB control measures in 1996 was followed by declining TST conversion rates, despite increasing exposure to active TB patients.

Setting: A provincial referral hospital in northern Thailand, where a cross-sectional study from 1995-1996 reported on the occupational risk of Mycobacterium tuberculosis transmission., Objective: To assess the impact of acid-fast bacilli sputum smear-positive results notification to improve tuberculosis (TB) services by documenting the location of sputum collection, completing the TB register immediately, and minimising delays between hospital admission and treatment initiation., Design: The cohort of smear-positive TB patients identified through laboratory microscopy record reviews from 1994-1999. Time from admission to hospital, laboratory diagnosis of TB, registration for treatment, and initiation of therapy were determined during the implementation of enhancing the laboratory results notification system., Results: The number of unregistered TB patients fell from 44 cases in 1994 to none in 1999. The time elapsed from admission to treatment initiation decreased from a mean of 5.6 days in 1997 (n = 162) to 3.1 days in 1999 (n = 136) (P < 0.001). This decrease was attributed to a reduction in time between laboratory diagnosis and treatment from 2.7 days in 1997 to 0.6 days in 1999 (P < 0.001)., Conclusion: Prompt identification, isolation and treatment of TB patients occurred through an enhanced laboratory notification system. Such systems are inexpensive, improve TB care services and may reduce nosocomial transmission of M. tuberculosis.

Objectives: To examine the association between HIV infection and tuberculosis (TB) and the proportion of TB attributable to HIV in Chiang Rai province, northern Thailand, in response to a rapidly changing incidence of HIV infection., Methods: Case-control study covering the period 1990 to 1998. Cases were all new TB patients seen at Chiang Rai Hospital. Controls were antenatal clinic attendees, delivery patients, surgical patients, blood donors, and military conscripts. Odds ratios (ORs) were calculated by year, age group, and sex, using each control group separately. The population attributable fraction was calculated by year., Results: During the study period, the number of new TB cases in Chiang Rai Hospital increased more than threefold. The ORs increased over time compared with all control groups for both sexes but did not vary consistently with age. The proportion of TB cases attributable to HIV rose to 72.0% in male patients and 65.8% in female patients by 1998., Conclusions: The HIV epidemic has a profound and prolonged impact on TB burden. Despite the marked reduction in HIV incidence already seen in Chiang Rai, the HIV prevalence among TB cases and the proportion of cases attributable to HIV continue to rise.

Injecting drug use and unsafe sexual practice are both considered major risk factors for HIV infection. This study reports sexual behaviors among male "current" (i.e. using heroin and/or opium at least once in the past 3 months) and "ex-" opiate users in Chiang Rai province in Northern Thailand. Between January 1999 and August 2000, 206 male opiate users were recruited by mail callback. Of the 206 drug users, 89 (43.2%) could be classified as current users. Current users did not differ from ex-users, except for educational level and ethnicity. Current and ex-opiate users showed no difference in number of regular sexual partners, proportion of having sex with commercial and non-commercial sex partners, and reported histories of sexually transmitted diseases. This study suggests that the importance of sexual risk behaviors in HIV transmission cannot be ignored in both current and ex-opiate users.

Setting: Chiang Rai Hospital, Chiang Rai Province, the epicentre of the human immunodeficiency virus (HIV) in Thailand., Objective: To describe the health seeking behaviour among tuberculosis (TB) patients, to measure patient and provider delays and to analyse factors determining these delays., Design: All patients aged over 15 years with new smear-positive pulmonary TB detected in Chiang Rai Hospital (n = 557) were interviewed using a structured questionnaire., Results: The median patient delays for HlV-positive and HIV-negative patients and those whose HIV status was unknown were 10, 15 and 15 days respectively, while provider delays were respectively 7, 7.5 and 10 days. HIV-positive patients suffered more symptoms and had a shorter patient's delay. Risk factors of long patient delay (>21 days) included being HIV-negative, having no health insurance, hill tribe ethnicity, no previous visits to the hospital, and borrowing money for hospital visits. Multivariate logistic analysis suggested that being married or widowed and being HIV-positive led to the shortest patient delay. Provider delay was significantly longer in female patients than male patients., Conclusion: Although patient and provider delays were favourably short, certain specific groups require further attention. Hill tribe people should be targeted to improve accessibility to TB treatment. Active case-finding services for people known to be HIV-positive should be encouraged. The reasons for the longer provider delay in female patients require further investigation.

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.

Focus groups were conducted in a high human immunodeficiency virus (HIV) prevalence area of Thailand to elicit perspectives of health staff and clients regarding the feasibility of directly observed therapy (DOT) for tuberculosis. Most participants perceived health centre-based DOT to be impractical for clients due to severe illness, travel inconvenience, and interference with employment. Most providers perceived home-based DOT to be difficult because of the inconvenience of travel, staff shortages and the high tuberculosis caseload. Most clients except HIV-negative tuberculous females considered home visits to be undesirable due to stigma. The preparedness of providers for home-based DOT might be improved through awareness building among staff about multidrug-resistant tuberculosis.

Setting: Chiang Rai Province in Northern Thailand, where human immunodeficiency virus (HIV) infection has been prevalent since the 1990s., Objective: To observe the prevalence of drug-resistant tuberculosis (TB) and investigate the factors related to the level of drug resistance in an HIV endemic area., Design: Population-based surveillance study covering the whole province., Method: Drug susceptibility testing was performed at the Thai Ministry of Public Health laboratory for all sputum smear-positive TB patients diagnosed in hospitals in Chiang Rai Province over a 25-month period in 1996-1998. Patient characteristics were obtained through interview by trained personnel. HIV testing was performed with informed consent., Results: Among the 1077 incident patients without previous history of treatment, the proportion of patients with resistance to isoniazid was 13.2%, 10.8% to rifampicin, 15.6% to streptomycin, and 5.8% to ethambutol. Multidrug resistance (MDR), i.e., resistance to at least both isoniazid and rifampicin, was observed in 6.3%. Factors associated with primary MDR-TB were HIV positivity (OR 2.2, 95%CI 1.3-3.9), age <50 years (OR 2.0), and treatment in the provincial hospital (OR 2.3), compared to patients treated in the community and private hospitals. Stratified analysis shows a significantly high prevalence of primary MDR-TB among HIV-positive patients treated in the provincial hospital against HIV-negative patients or HIV-positive patients in other hospitals., Conclusion: The prevalence of primary MDR-TB in this area was high. It is necessary to strengthen TB control activities in order to reduce the burden of MDR-TB.

Objectives: To determine trends and associated risk factors of HIV incidence (1989-1997) in a drug abuse treatment clinic in northern Thailand where HIV is epidemic., Design: Retrospective cohort study., Methods: Nine-years (1989-1997) of data (excluding names) from the logbook of drug abusers seeking treatments in Mae Chan Hospital in Chiangrai Thailand, were transcribed and double-entered into separate computer files which were later validated against each other. For each patient, the dates of the first HIV negative, the last HIV negative, and the first HIV positive were determined. A retrospective cohort of drug users who were initially HIV-negative and treated for more than once was constructed. HIV seroconversion was assumed to follow a uniform distribution between the last negative and the first positive HIV tests. The incidence rates and their 95% confidence intervals (CI) were calculated., Results: Of the 378 repeat patients, 16 (4.2%) HIV seroconverted. This is equivalent to 5.11 per 100 person-years of observation (PYO) (95% CI = 3.13-8.35). The incidence remained relatively stable over the study period while the prevalence was on the decline. The younger, Thai lowlanders, drug injectors had higher incidence rates than the older, ethnic minorities and drug smokers, respectively., Conclusion: Prevalence can give illusional results. It is necessary to know baseline HIV incidence to monitor and evaluate an HIV intervention program.

Setting: Chiang Rai, the northernmost province of Thailand, where extensive human immunodeficiency virus (HIV) transmission has resulted in a rapid increase in tuberculosis., Objective: To assess the utility of tuberculin and anergy skin testing to identify latent Mycobacterium tuberculosis infection in HIV-infected persons., Design: A cross-sectional study and analysis were conducted to examine reactivity to tuberculin and two control antigens (mumps and candida) in HIV-negative and HIV-positive blood donors and female sex workers., Results: HIV-positive persons had markedly decreased tuberculin reactivity; 14%, 19%, and 40% had an induration of > or = 10 mm, > or = 5 mm, > or = 2 mm, respectively, while 51% of 525 HIV-negative persons had an induration of > or = 10 mm (P < 0.001). Mumps and candida positivity (reactions of > or = 3 mm) were found in 94% and 78% of HIV-negative persons compared with 72% and 61% of HIV-positive persons, respectively (P < 0.001). Although HIV-positive persons had markedly less tuberculin reactivity even at higher CD4+ cell counts (> 400 cells/microL), reactivity to mumps and candida was present in more than half of HIV-positive persons with low CD4+ cell counts (< or = 200 cells/microL). Reaction to control antigens did not predict tuberculin reactivity., Conclusion: In this setting, tuberculin and anergy skin testing have a low predictive value in detecting M. tuberculosis infection in HIV-infected persons, and therefore such testing has a limited role in identifying HIV-infected persons who may benefit from tuberculosis preventive therapy programs.

Objective: To determine the level of and reasons associated with adherence to tuberculosis preventive therapy among asymptomatic HIV-infected individuals in northern Thailand., Design: A prospective cohort study with a 9-month follow-up., Methods: A total of 412 HIV-infected persons were enrolled in a tuberculosis preventive therapy programme in a hospital. A 9-month isoniazid regimen was prescribed. Adherence was determined by pill count. Participants who missed a scheduled appointment for more than a month were interviewed. Five focus group discussion sessions were held among those who successfully completed the therapy., Results: Of the 412 participants, 69.4% (286) completed the 9-month regimen. The adherence rate, defined as the proportion of those who took more than 80% of pills, was 67.5% (n = 278). Sex, source of participants and history of physical symptoms were associated with adherence. A significant portion of defaults took place at the beginning of the therapy. Out-migration, denial of HIV status, and perceived side effects of isoniazid were frequently cited as reasons for non-adherence. For those adhering participants, the acceptance of personal HIV status, concern about children and family, and a good health provider relationship were important reasons motivating adherence. Several reminder systems were developed by the participants., Conclusions: Although a isoniazid preventive therapy programme was shown to be feasible, further adjustments on the selection of participants, enrollment process, and follow-up system based on these findings are necessary to increase the adherence.

Despite mandatory antibody testing, human immunodeficiency virus (HIV) can be transmitted from HIV-infected blood that is seronegative. The objective of this study was to estimate the probability of HIV-infected blood donations during the seronegative "window period" in a northern Thailand HIV epicenter. Thus, a retrospective cohort of repeat blood donors was created. With the assumptions that the probability of HIV seroconversion is distributed uniformly between the last HIV-negative and the first HIV-positive donation and that the seronegative window is 45 days, the rate of window-period donations was calculated by multiplying the incidence by the window duration. Of 11,232 repeat donors, 273 seroconverted during 9,518,863 person-days of observation (i.e., a window-period donation rate of 1/775). There were more window-period donations among 21- to 30-year-old men and in donors replacing blood of friends or relatives. Additional measures are needed to reduce the high number of HIV-infected window-period donations.

Objective: Chiang Rai, the northernmost province of Thailand, has experienced an explosive HIV epidemic since 1989. This study assessed the impact of HIV infection on tuberculosis (TB) in the area., Methods: We analyzed the incidence of reported TB in the province from 1982 through 1993 and TB registry data at Chiang Rai Hospital from 1985 through 1994., Results: Following a steady decline in reported TB from 1982 through 1991, the incidence of TB increased sharply after 1991. TB registry data from Chiang Rai Hospital, which began confidential HIV testing in October 1989, indicated a steady and rapid increase in the number and proportion of HIV-seropositive TB patients from four (1.5% of all TB patients) in 1990 to 207 (45.5%) in 1994 (P < 0.001). Compared with HIV-negative TB patients, HIV-positive TB patients were more likely to be men, aged 20-39 years and have extrapulmonary TB (P < 0.001). Treatment completion rates were similar. Twelve months after beginning TB treatment, HIV-positive TB patients had a mortality rate of 68.6% [95% confidence interval (Cl), 62.7-74.3] compared with 10.0% (95% Cl, 8.3-12.1%) in HIV-negative patients (P < 0.001)., Conclusion: Thailand and other Asian countries where HIV is spreading rapidly must promptly address the dual epidemic of TB and HIV in order to reduce preventable morbidity and mortality.

Background: The purpose of this study was to develop human immunodeficiency virus (HIV) infection donation deferral criteria for blood donors in an HIV-epidemic area of northern Thailand, where the predominant means of transmission of HIV is through heterosexual contact., Study Design and Methods: In a preliminary study, 2242 blood donors were interviewed, and their blood was tested for HIV antibodies between September 1993 and April 1994. The risk factors associated with HIV positivity were identified. Criteria to identify HIV-positive persons on the basis of a logistic equation were developed and applied to another group of 5769 prospective blood donors., Results: A multivariate analysis showed the following odds ratios (OR) for traits that were independently associated with HIV positivity: younger age (OR = 0.93 for each additional year of age), male gender (OR = 2.41), having no more than a primary school education (OR = 2.00), being in the military (OR = 1.78), being unsure of one's own blood safety (OR = 2.00), history of injecting drug use (OR = 5.36), diagnosis of syphilis or positive syphilis serologic test in the past 12 months (OR = 2.67), and genital ulcer in the past 12 months (OR = 4.56). On the basis of the model, with a limit of <10 percent loss of uninfected donors, predicted probabilities of HIV positivity alone or of markers of infection with HIV, hepatitis B virus, or Treponema pallidum were calculated. With a cutoff of 6.5-percent estimated probability of HIV infection, derived from the logistic equation, the donor deferral criteria have 33.6-percent sensitivity and 8.3-percent positive predictive value for HIV positivity and 15.5-percent sensitivity and 18.4-percent positive predictive value for markers of infection with one of the three pathogens., Conclusion: The proposed donor deferral system provides a more flexible, sensitive, and predictive tool for averting donation by those who, though HIV antibody-negative, are at a higher risk of being infected with HIV.