Ergotism in Thailand caused by increased access to antiretroviral drugs: a global warning.

Ergotism is a toxic condition resulting from overexposure to the ergot compounds produced by various fungi of the genus Claviceps. Traditionally, such exposure was due to ingestion of infected grains, but long-term or excessive use of medications containing ergot derivatives or drug-drug interactions between these medications can result in ergotism. Ergotamine, typically used to treat migraine, has less than 5% bioavailability due to extensive first-pass metabolism by cytochrome P450 3A4 (CYP3A4). Concurrent intake of ergotamine and strong CYP3A4 inhibitors, such as the HIV protease inhibitors (PIs), can lead to clinical ergotism. A total of 13 cases of clinical ergotism in HIV-infected patients has been published since 1997 (most recently reviewed by Frohlich et al).

Genome-wide association studies of tuberculosis in Asians identify distinct at-risk locus for young tuberculosis.

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.

Diagnostic value of two rapid immunochromatographic tests for suspected tuberculosis diagnosis in clinical practice.

OBJECTIVE: To evaluate and compare the diagnostic value of two immunochromatographic tests for tuberculosis (ICT-TB) in clinical practice. MATERIAL AND METHOD: The present extended cross-sectional study investigated suspected active TB patients at Maesai district hospital, and Lampang regional hospital between April 2009 and May 2010. Subjects underwent two commercial ICT-TB serum tests including: an endogenous ICT-TB, a local made test coated with 38 kD, 16 kD, and 6 kD antigens; and an exogenous ICT-TB, an imported test coated with 38 kD and lipoarabinomanan [LAM] antigens. All subjects received two months of follow up. RESULTS: Of 401 patients, 146 (36.4%) had active TB, and 206 (51.4%) were HIVseropositive. An endogenous ICT-TB was superior to an exogenous ICT-TB in all diagnostic values measured except for specificity. In all patients, sensitivity was low, 35.6% (95% CI: 30.9-40.3) in an endogenous ICT-TB vs. 13.7% (95% CI: 10.3-17.1) in an exogenous ICT-TB. The specificity was high and equivalent in both tests, 93.7% (95%CI: 91.4-96.1). Higher diagnostic values were found among human immunodeficiency virus (HIV) seronegatives than in HIV seropositives when unadjusted for CD4+ cell count level. The likelihood ratios (LHR) were higher in patients with CD4+ cell count over 200 cells/microL than for the HIV seronegative group (LHR+ 7.6 vs. 4.8 in an endogenous ICT-TB, and 2.5 vs. 1.9 in an exogenous ICT-TB). CONCLUSION: For the present study setting, an endogenous ICT-TB can be a meaningful tool for first-line testing to rule in TB suspected cases. Subgroups of HIV seronegative and HIV seropositive patients with CD4+ cell count over 200 cells/microL may be expected to benefit most from the test.

Diagnostic value of an immunochromatographic test over clinical predictors for tuberculosis in HIV patients.

PURPOSE: The value of an immunochromatographic test for tuberculosis (ICT-TB) combined with clinical predictors has yet to be evaluated in Thailand. This study aimed to assess any additional diagnostic value of an ICT-TB test over that of clinical predictors in a group of human immunodeficiency virus (HIV) patients as well as in subgroups of HIV patients classified by clinical risk scores. PATIENTS AND METHODS: An extended cross-sectional study was conducted at a community hospital in Chiang Rai and a general hospital in Lampang. HIV patients registered between April 2009 and May 2010 were screened by a locally made ICT-TB test, including 38, 16, and 6 kD Microbacterium tuberculosis antigens, as well as by routine evaluations for TB diagnosis. Demographic data, medical history, signs, and symptoms were recorded. Participants were followed up for 2 months for final ascertainment of TB diagnosis. RESULTS: Of 206 patients, 37 (18%) had TB. Four clinical predictors were identified: low body mass index (<19 kg/m(2)), prolonged cough (duration >2 weeks), shaking chills (≥1 week), and no use of antiretrovirals. The area under the receiver operating curve was 90.2%; adding the ICT-TB test result increased the area nonsignificantly to 91.6% (P = 0.40). When patients were categorized by risk scores derived from selected clinical predictors into low (scores ≤7) and high (scores >7) TB risk groups, a positive ICT-TB test increased the positive predictive value nonsignificantly in the low risk group (from 12.5% to 27.3%, P = 0.17) and the high risk group (from 78.6% to 80.8%, P = 0.73). CONCLUSION: In this study setting, the ICT-TB test did not enhance TB diagnosis over the four clinical predictors in the overall group or any subgroups of HIV patients classified by clinical risk scores.

Screening scheme development for active TB prediction among HIV-infected patients.

The objective of this study was to develop and evaluate a simple scoring scheme to screen for active tuberculosis (TB) among HIV-infected patients. Two hundred fifty-seven HIV-infected patients were enrolled in the study between April 2009 and May 2010 from Mae Sai District Hospital and Lampang Regional Hospital. Participants underwent routine evaluations to diagnose TB. Data collection included demographics, medical history, signs and symptoms and laboratory results. Of the 257 HIV-infected patients enrolled, 66 (25.7%) were diagnosed with active TB. Six variables were statistically significant predictors of active TB (p < 0.05): BMI < or = 19 kg/m2, cough > 2 weeks, shaking chills > or = 1 week not taking antiretroviral drugs, a CD4+ cell count level < 200 cells/microl, and had a history of TB. A risk score (ranging from 0 to 16) gave a 92.1% sensitivity of being associated with active TB. A low risk score (< or = 2.0), a moderate risk score (3.0-7.0), and a high risk score (>7.0) gave positive likelihood ratios (LHR+) of 0.04 (95% CI 0.01-0.24), 2.56 (95% CI 1.71-3.85), and 11.72 (95% CI 4.91-27.96), respectively. This screening tool may be useful to identify patients who should have further diagnostic testing for TB, but requires further validation before adoption due to the variability of predicting factors and the prevalence of TB in the target population.