Search

Introduction: Odesa province has the highest TB/HIV prevalence in Ukraine, exceeding the total prevalence in the country by 3 times. The objective of this study was to investigate the unfavorable treatment outcomes and associated factors in patient with drug-resistant (DR) TB in people living with HIV (PLH) in Odesa., Methodology: A cohort study with secondary data analysis was conducted among 373 PLH with confirmed pulmonary DR TB for 2014-2016., Results: About 2/3rd of the cohort were males from urban areas. Mean age and CD4 counts were 39 and 203, respectively. The overall treatment success was 44.2% with the most unfavorable treatment outcomes being observed in extensively and pre-extensively drug resistant (XDR and PreXDR) TB. The mean time between the results of GeneXpert (manufactured by Cepehid) and DR TB treatment based on GeneXpert was 1.3 days. However, the mean time between DR TB treatment based on GeneXpert and results of drug susceptibility test (DST) was 37.0 days referring to a late reporting of DST and to a late adjustment of previously prescribed treatment. The factors associated with the treatment unfavorable outcome included XDR and Pre-XDR TB, lack of antiretroviral treatment (ART), contrimoxazole preventive therapy (CPT) and CD4 test., Conclusions: The rate of successful DR TB treatment in PLH in Odesa remains low. The delayed reporting of DST contributes to lack of timely adjusted treatments. XDR and Pre-XDR TB, lack of ART and CPT are associated with unfavorable treatment outcomes. Additional studies would help to understand the temporal relationship between CD4 test and treatment outcomes., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Svitlana Yesypenko, Ruzanna Grigoryan, Yulia Sereda, Olga Denisuk, Liana Kovtunovich, Tatyana Rybak, Oleksandr Postnov, Oleksandr Neduzhko, Sergiy Antonyak, Valentina Bespoyasnaya.)

Background: Drug resistance is a key obstacle to the global target set to end tuberculosis by 2030. Clinical complexities in drug-resistant tuberculosis and HIV-infection co-management could worsen outcomes of second-line anti-tuberculosis drugs. A comprehensive estimate for risks of unsuccessful outcomes to second-line tuberculosis therapy in HIV-infected versus HIV-uninfected patients is mandatory to address such aspects in segments of the target set. Therefore, this meta-analysis was aimed to estimate the pooled risk ratios of unfavorable outcomes to second-line tuberculosis therapy between HIV-infected and HIV-uninfected patients in sub-Saharan Africa., Methods: We conducted a literature search from PubMed/MEDLINE, EMBASE, SCOPUS and Google Scholar. We screened the retrieved records by titles and abstracts. Finally, we assessed eligibility and quality of full-text articles for the records retained by employing appraisal checklist of the Joanna Briggs Institute. We analyzed the data extracted from the included studies by using Review Manager Software, version 5.3 and presented our findings in forest and funnel plots. Protocol for this study was registered on PROSPERO (ID: CRD42020160473)., Results: A total of 19 studies with 1,766 from 4,481 HIV-infected and 1,164 from 3,820 HIV-uninfected patients had unfavorable outcomes. The risk ratios we estimated between HIV-infected and HIV-uninfected drug-resistant tuberculosis patients were 1.18 (95% CI: 1.07-1.30; I2 = 48%; P = 0.01) for the overall unfavorable outcome; 1.50 (95% CI: 1.30-1.74) for death; 0.66 (95% CI: 0.38-1.13) for treatment failure; and 0.82 (95% CI: 0.74-0.92) for loss from treatment. Variable increased risks of unfavorable outcomes estimated for subgroups with significance in mixed-age patients (RR: 1.22; 95% CI: 1.10-1.36) and eastern region of sub-Saharan Africa (RR: 1.47; 95% CI: 1.23-1.75)., Conclusions: We found a higher risk of unfavorable treatment outcome in drug-resistant tuberculosis patients with death highly worsening in HIV-infected than in those HIV-uninfected patients. The risks for the unfavorable outcomes were significantly higher in mixed-age patients and in the eastern region of sub-Saharan Africa. Therefore, special strategies that reduce the risks of death should be discovered and implemented for HIV and drug-resistant tuberculosis co-infected patients on second-line tuberculosis therapy with optimal integration of the two programs in the eastern region of sub-Saharan Africa., Competing Interests: The authors have declared that no competing interests exist.

Background: Tuberculosis (TB) is a public health concern, especially in resource-constrained countries like Cameroon. TB drug resistance is a major obstacle to control and prevent., Design: Data from 2014 to 2016 on the outcome of anti-TB treatment in the Littoral Region were reviewed manually and analysed using the meta-analysis concept. The treatment success rates (TSR) were the primary outcome used for this study. The heterogeneity statistics ( I 2 ) was computed to orientate the choice of the best statistical model (binary fixed effect or random) to compute pooled value of TSR., Results: Using an intention-to-treat analysis, the pooled proportions of HIV-uninfected TB patients successfully cured from TB were low and slightly decreased by 1% between 2014 and 2016. Regarding HIV-infected TB patients, pooled values of TSR were lower than those of their HIV-negative counterparts with values ranging from 71% (95% CI: 63%-83%; I 2 = 71.16%) in 2014 to 68% (95% CI: 58%-79%; I 2 = 70.97%) in 2016. In addition, no heterogeneity was found in three years ( I 2 = 0.0%; P value = 1). These cure rates were strongly and negatively correlated with the rates of patients lost to follow-up regardless of the year. In HIV-infected patients, the pooled values of ITT analysis-based treatment success rates were 73% ( χ 2 = 13.92, P value = 0.0002), 71% ( χ 2 = 7.26, P value = 0.007), and 68% ( χ 2 = 8.02, P value = 0.004), respectively. The coverage rates with cotrimoxazole (CTX) gradually increased over year ranging from 78.90% in 2014 to 94.17% in 2016, similar to the coverage rate for ARV therapy that was 60.06% in 2014 against 90% in 2016. A positive and statistically significant correlation was found between the success of the anti-TB therapy in HIV-infected patients and coverage rates with CTX and ARV., Conclusion: An improvement in the reduction of percentage of lost to follow-up and coverage with CTX and ARV therapy could greatly increase chances to efficiently control TB in Cameroon., Competing Interests: The authors declare having no competing interest., (Copyright © 2020 Dorgelesse F. Kouemo Motse et al.)

Objective: Multidrug-resistant tuberculosis (MDR-TB) remains a serious public health problem worldwide. Accordingly, this study sought to identify individual, community and access to health services risk factors for MDR-TB., Methods: Retrospective cohort of all TB cases diagnosed between 2006 and 2016 in the state of São Paulo. A Bayesian spatial hierarchical analysis with a multilevel design was carried out., Results: It was identified that the history of previous TB treatment (Odds Ratios [OR]:13.86, 95% credibility interval [95% CI]:12.06-15.93), positive sputum culture test (OR: 5.26, 95% CI: 4.44-6.23), diabetes mellitus (OR: 2.34, 95% CI: 1.87-2.91), residing at a standard address (OR: 2.62, 95% CI: 1.91-3.60), positive sputum smear microscopy (OR: 1.74, 95% CI: 1.44-2.12), cavitary pulmonary TB (OR: 1.35, 95% CI: 1.14-1.60) and diagnosis performed due to spontaneous request (OR: 1.26; 95% CI: 1.10-1.46) were associated with MDR-TB. Furthermore, municipalities that performed HIV tests in less than 42.65% of patients with TB (OR: 1.50, 95% CI: 1.25-1.79), that diagnosed TB cases only after death (OR: 1.50, 95% CI: 1.17-1.93) and that had more than 20.16% of their population with income between ¼ and ½ of one minimum wage (OR: 1.56, 95% CI: 1.30-1.87) were also related to the MDR-TB., Conclusions: Knowledge of these predictive factors may help to develop more comprehensive disease prevention strategies for MDR-TB, avoiding the risks expressed regarding drug resistance expansion., (© 2020 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objective: Tuberculosis (TB) is the leading cause of adrenal insufficiency in resource-limited settings. The adrenal gland is the most commonly affected endocrine organ in TB infection. We assessed factors associated with functional adrenal insufficiency (FAI) among TB-HIV patients with and without drug-resistance in Uganda. Patients with drug-sensitive and drug-resistant TB were enrolled and examined for clinical signs and symptoms of FAI with an early morning serum cortisol level obtained. FAI was defined as early morning serum cortisol < 414 nmol//L. Associations with FAI were modeled using multivariable logistic regression., Results: We screened 311 TB patients and enrolled 272. Of these, 117 (43%) had drug-resistant TB. Median age was 32 years (IQR 18-66) and 66% were men. The proportion with FAI was 59.8%. Mean cortisol levels were lower in participants with drug-resistant than susceptible TB (317.4 versus 488.5 nmol/L; p < 0.001). In multivariable analyses, drug-resistant TB (aOR 4.61; 95% CI 2.3-9.1; p < 0.001), treatment duration > 1 month (aOR 2.86; 95% CI 1.4-5.5; p = 0.002) and abdominal pain (aOR 2.06; 95% CI 1.04-4.09; p = 0.038) were significantly associated with FAI. Early morning serum cortisol levels should be quantified in TB-HIV co-infected patients with drug-resistant TB.

Background: Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective., Cases Presentation: In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB., Conclusions: We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

Tuberculosis (TB) is common among persons living with HIV. This public health concern is aggravated by infection with multidrug-resistant organisms and adverse effects of polypharmacy. There are few published cases of multidrug-resistant tuberculosis (MDR-TB) in multidrug-resistant HIV (MDR-HIV) infected patients. We report a case of a 29-year-old Filipino man with HIV on zidovudine (AZT)-containing antiretroviral therapy (ART) but was eventually shifted to tenofovir due to anaemia. He presented with left flank tenderness, which was found to be due to an MDR-TB psoas abscess, and for which second-line anti-TB treatment was started. HIV genotyping showed MDR-HIV infection susceptible only to AZT, protease inhibitors and integrase inhibitors. Subsequently, he developed neck abscess that grew Mycobacterium avium complex and was treated with ethambutol and azithromycin. ART regimen was revised to AZT plus lamivudine and lopinavir/ritonavir. Erythropoietin was administered for recurrent AZT-induced anaemia. Both abscesses resolved and no recurrence of anaemia was noted., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

HIV-positive adults on treatment for multi drug-resistant tuberculosis (MDR-TB) experience high mortality. Biomarkers of HIV/MDR-TB treatment response may enable earlier treatment modifications that improve outcomes. To determine whether changes in C-reactive protein (CRP), D-dimer, and fibrinogen were associated with treatment outcome among those with HIV/MDR-TB coinfection, we studied 20 HIV-positive participants for the first 16 weeks of MDR-TB therapy. Serum CRP, fibrinogen, and D-dimer were measured at baseline and serially while on treatment. At baseline, all biomarkers were elevated above normal levels, with median CRP 86.15 mg/L (interquartile range [IQR] 29.25-149.32), D-dimer 0.85 µg/mL (IQR 0.34-1.80), and fibrinogen 4.11 g/L (IQR 3.75-6.31). C-reactive protein decreased significantly within 10 days of treatment initiation and fibrinogen within 28 days; D-dimer did not change significantly. Five (25%) participants died after a median of 32 days. Older age (median age of 38 y among survivors and 54 y among deceased, P = 0.008) and higher baseline fibrinogen (3.86 g/L among survivors and 6.37 g/L among deceased, P = 0.02) were significantly associated with death. After adjusting for other measured variables, higher CRP concentrations at the beginning of each measurement interval were significantly associated with a higher risk of death during that interval. Trends in fibrinogen and CRP may be useful for evaluating early response to treatment among individuals with HIV/MDR-TB coinfection.

Background: Mortality in multidrug-resistant (MDR) tuberculosis-human immunodeficiency virus (HIV) coinfection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR tuberculosis-HIV-coinfected patients on ART to those in patients with MDR tuberculosis alone., Methods: This observational study enrolled culture-confirmed MDR tuberculosis patients with and without HIV in South Africa between 2011 and 2013. Participants received standardized MDR tuberculosis and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival., Results: Among 206 participants, 150 were HIV infected, 131 (64%) were female, and the median age was 33 years (interquartile range [IQR], 26-41). Of the 191 participants with a final MDR tuberculosis outcome, 130 (73%) were cured or completed treatment, which did not differ by HIV status (P = .50). After 2 years, CD4 count increased a median of 140 cells/mm3 (P = .005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; P = .34). The strongest risk factor for mortality was having a CD4 count ≤100 cells/mm3 (adjusted hazards ratio, 15.6; 95% confidence interval, 4.4-55.6)., Conclusions: Survival and treatment outcomes among MDR tuberculosis-HIV individuals receiving concurrent ART approached those of HIV-uninfected patients. The greatest risk of death was among HIV-infected individuals with CD4 counts ≤100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR tuberculosis and HIV.

Lopinavir-ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir-ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir-ritonavir and drugs routinely used for MDR-TB treatment in HIV-infected children. A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 with MDR-TB receiving treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin and 16 without TB) who were established on a lopinavir-ritonavir-containing antiretroviral regimen. One-compartment models with first-order absorption and elimination for both lopinavir and ritonavir were combined into an integrated model. The dynamic inhibitory effect of the ritonavir concentration on lopinavir clearance was described using a maximum inhibition model. Even after adjustment for the effect of body weight with allometric scaling, a large variability in lopinavir and ritonavir exposure, together with strong correlations between the pharmacokinetic parameters of lopinavir and ritonavir, was detected. MDR-TB treatment did not have a significant effect on the bioavailability, clearance, or absorption rate constants of lopinavir or ritonavir. Most children (81% of children with MDR-TB, 88% of controls) achieved therapeutic lopinavir trough concentrations (>1 mg/liter). The coadministration of lopinavir-ritonavir with drugs routinely used for the treatment of MDR-TB was found to have no significant effect on the key pharmacokinetic parameters of lopinavir or ritonavir. These findings should be considered in the context of the large interpatient variability found in the present study and the study's modest sample size., (Copyright © 2018 American Society for Microbiology.)

Antimicrobial drug resistance creates major problems in the control of tuberculosis (TB). Beijing and Haarlem genotypes of Mycobacterium tuberculosis are the prevalent genotypes responsible for multidrug resistant (MDR) TB worldwide. The aim of this study was to conduct a systematic review using meta-analysis to indicate the prevalence of Beijing and Haarlem genotypes among MDR-TB cases in Iran. Data sources of current study were 311 original articles (2006-2016) that were searched in several databases including Medline, Scopus, Embase, Cochrane library, and Iranian databases. Sixteen articles were selected for the prevalence of Beijing and Haarlem families among MDR-TB strains. Data were evaluated using meta-analysis and random effects models with the Meta-Analysis Software package Version 2.2 (Biostat, Englewood, NJ). Final investigation indicated 856 MDR samples in the 16 articles. Overall, the prevalence of Beijing and Haarlem genotypes among MDR-TB isolates in Iran was estimated to be 19.3% (95% CI, 13.1-27.5) and 18.7% (95% CI, 11.9-28.3) respectively. The studies conducted in northern Iran showing a significant association between Haarlem genotype and MDR is of particular concern. Certain refugee migration flows make this genotype of particular epidemiological and clinical concern because of its potential ability to endanger TB control programs in Iran., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Delayed diagnosis of tuberculosis (TB) and drug-resistant TB are major challenges of TB control in Thailand. This study assessed the practicality of the Xpert MTB/RIF assay in a real-life setting with high prevalence of human immunodeficiency virus (HIV) infection and pulmonary tuberculosis (PTB)., Methods: This prospective study was conducted at 3 large tertiary care hospitals. Patients who had suspected PTB were enrolled into the study. Expectorated sputum samples were sent for staining, mycobacterial culture, and Xpert MTB/RIF., Results: Four hundred ninety-four patients were enrolled. From 355 cases with final diagnosis of PTB, 263 (71.8%) had definite diagnosis and 92 cases had probable diagnosis. Among TB culture-positive cases, Xpert MTB/RIF had 100% and 81% sensitivity in sputum smear-positive and smear-negative groups, respectively. The specificity was 95.7%. The sensitivity and positive predictive value of Xpert MTB/RIF in culture-negative but clinically diagnosed PTB was 37.8% and 83.8%, respectively. Centrifugation was required in 59% cases with scanty sputum. Five cases were false-positive by Xpert MTB/RIF in patients with nontuberculous mycobacteria, old PTB scar, and immune reconstitution syndrome. Discordant rifampicin susceptibility results of Xpert MTB/RIF and mycobacteria growth indicator tube (MGIT) were confirmed by using rpoB gene sequencing, which raised the sensitivity of Xpert MTB/RIF in detecting rifampicin resistance to 93.8%., Conclusions: Xpert MTB/RIF is an effective tool in diagnosing PTB but will be more cost-effective for sputum-negative patients and in settings with high prevalence of rifampicin resistance. Early diagnosis of TB results in early treatment and implementation of strategies to limit spreading of TB. Sputum centrifugation may increase the yield of Xpert MTB/RIF., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the incidence of tuberculosis (TB) globally, posing a formidable global health challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance in the programmatic perspective as it is readily transmissible as well as easily diagnosable. HIV complicates every aspect of pulmonary tuberculosis from diagnosis to treatment, demanding a different approach to effectively tackle both the diseases. In order to control these converging epidemics, it is important to diagnose early, initiate appropriate therapy for both infections, prevent transmission and administer preventive therapy. Liquid culture methods and nucleic acid amplification tests for TB confirmation have replaced conventional solid media, enabling quicker and simultaneous detection of mycobacterium and its drug sensitivity profile Unique problems posed by the syndemic include Acquired rifampicin resistance, drug-drug interactions, malabsorption of drugs and immune reconstitution inflammatory syndrome or paradoxical reaction that complicate dual and concomitant therapy. While the antiretroviral therapy armamentarium is constantly reinforced by discovery of newer and safer drugs every year, only a few drugs for anti tuberculosis treatment have successfully emerged. These include bedaquiline, delamanid and pretomanid which have entered phase III B trials and are also available through conditional access national programmes. The current guidelines by WHO to start Antiretroviral therapy irrespective of CD4+ cell count based on benefits cited by recent trials could go a long way in preventing various complications caused by the deadly duo. This review provides a consolidated gist of the advancements, concepts and updates that have emerged in the management of HIV-associated pulmonary TB for maximizing efficacy, offering latest solutions for tackling drug-drug interactions and remedial measures for immune reconstitution inflammatory syndrome.

Translating the potential of Xpert(®) MTB/RIF into more effective tuberculosis (TB) care and control in low-income settings is challenged by operational issues. We report the experience in introducing this technology in Burkina Faso through a centralised approach. Xpert was successfully integrated into the diagnostic algorithm of multidrug-resistant TB cases. However, barriers to Xpert use for the diagnosis of TB in vulnerable populations, such as persons living with human immunodeficiency virus infection and children, were observed, mainly due to lack of coordination between services. Lessons learnt can be exploited to optimise the roll-out of this technology at country level.

Phenotypic culture-based drug susceptibility testing (DST) for Mycobacterium tuberculosis is a valuable tool to identify four to six active drugs for individualized multidrug-resistant (MDR) tuberculosis (TB) regimens. Current culture-based methods are slow, however; therefore, we evaluated a rapid mycobacteriophage-based quantitative PCR (qPCR) assay for use directly on M. tuberculosis-positive MGIT broths. We compared phage qPCRs, using a simple cutoff of 3 for the ΔCq value (where Cq is quantification cycle, and ΔCq is calculated as the Cq of starting phage minus the Cq of TB isolates in drug-containing medium), on 325 clinical M. tuberculosis MGIT broth cultures versus the respective subcultured isolates tested by agar proportion. The median accuracy for the 13 drugs/concentrations tested was 98%, with most discrepancies being false-resistant results. Evaluation of phage qPCR on greater numbers of resistant strains of 393 isolates grown on Löwenstein-Jensen medium showed similar findings, with a median accuracy, sensitivity, and specificity of 97%, 90%, and 99%, respectively. This rapid culture-based DST methodology can be performed for any drug on TB-positive MGIT broths, with a specimen-to-antibiogram turnaround time of approximately 23.9 days, compared with waiting 58.6 days for isolate growth on solid medium followed by agar proportion DST.

Background: Evidence is limited to guide the management of children exposed to multidrug-resistant (MDR) tuberculosis. We aimed to study the tolerability and toxicity of a standard preventive therapy regimen given to children exposed to infectious MDR tuberculosis, and explore risk factors for poor outcome., Methods: In this prospective cohort study in the Western Cape, South Africa, children <5 years of age, or human immunodeficiency virus (HIV)-positive children aged <15 years, were recruited from May 2010 through April 2011 if exposed to an ofloxacin-susceptible, MDR tuberculosis source case. Children were started on preventive therapy as per local guidance: ofloxacin, ethambutol, and high-dose isoniazid for 6 months. Standardized measures of adherence and adverse events were recorded; poor outcome was defined as incident tuberculosis or death from any cause., Results: One hundred eighty-six children were included, with a median age of 34 months (interquartile range, 14-47 months). Of 179 children tested for HIV, 9 (5.0%) were positive. Adherence was good in 141 (75.8%) children. Only 7 (3.7%) children developed grade 3 adverse events. One child (0.5%) died and 6 (3.2%) developed incident tuberculosis during 219 patient-years of observation time. Factors associated with poor outcome were age <1 year (rate ratio [RR], 10.1; 95% confidence interval [CI], 1.65-105.8; P = .009), HIV-positive status (RR, 10.6; 95% CI, 1.01-64.9; P = .049), exposure to multiple source cases (RR, 6.75; 95% CI, 1.11-70.9; P = .036) and poor adherence (RR, 7.50; 95% CI, 1.23-78.7; P = .026)., Conclusions: This 3-drug preventive therapy regimen was well tolerated and few children developed tuberculosis or died if adherent to therapy. The provision of preventive therapy to vulnerable children following exposure to MDR tuberculosis should be considered.

Introduction: In settings such as Namibia with a high prevalence of human immunodeficiency virus (HIV) and drug-resistant (DR) tuberculosis (TB) co-infection, interactions and adverse events associated with second-line anti-TB and antiretroviral medicines pose a unique challenge in the treatment of both infections., Objective: The main objective of this study was to compare the absolute risks and risk factors for commonly observed adverse events (occurring in >20 % of patients) during DR-TB treatment in HIV-infected and HIV-uninfected patients., Methods: This was a retrospective cohort analysis of patients treated for DR-TB between January 2008 and February 2010 at the Kondja DR-TB ward in Walvis Bay, Namibia. Data were anonymously collected from patients' treatment records, using a structured form. The data were then analyzed using descriptive statistics, while 2 × 2 contingency tables stratified by HIV status were employed to examine specific risk factor and adverse event relationships, using Epi Info 3.4.3 statistical software. Eighteen adverse events were studied but, because of the small sample size of patients, only the four most frequent ones (occurring in >20 % of patients) were included in the risk factor analysis. The risk factors were a treatment period of <4 weeks; treatment with any highly active antiretroviral therapy (HAART) regimen; specific treatment with a zidovudine (AZT)-based HAART regimen, a cycloserine-based DR-TB regimen or an amikacin-based DR-TB regimen; female gender; baseline body weight ≤ 45 kg; and age 30 ≥ years., Results: Of the 57 DR-TB patients who were included in the analysis, 31 (53 %) were co-infected with HIV. When stratified by HIV status, DR-TB patients had similar exposure to specific DR-TB medicines and comparable demographic and clinical characteristics, except for age, as HIV-infected patients were on average 6.5 years older than HIV-uninfected patients (P = 0.007). Of the 18 studied adverse events, tinnitus (40 %), joint pain (26 %), hearing loss (23 %) and nausea (21 %) were the four most commonly observed events. Only for abdominal pain was there a statistically significant difference in the risk of occurrence between HIV-infected patients and HIV-uninfected patients (26 versus 4 %, P = 0.02). The risk ratios (RRs) for the association between treatment with a cycloserine-based DR-TB regimen and occurrence of joint pain did not differ much between HIV-infected and HIV-uninfected patients (RR 4.3 in HIV-infected patients, P = 0.03; RR 5 in HIV-uninfected patients, P = 0.08). Similarly, although some differences in the RRs were observed between the two HIV status groups, the differences were not statistically significant for tinnitus, hearing loss or nausea. In some instances, HIV status appeared to modify the effect of the association of some of the risk factors and adverse event occurrence, but the wide and overlapping confidence intervals were inconclusive., Conclusion: Generally, the absolute risks and risk factors for adverse events were similar between HIV-infected and HIV-uninfected patients treated for DR-TB in our Namibian cohort of 57 patients. Although our findings of comparable adverse event risks between DR-TB and DR-TB/HIV co-infected patients are encouraging, they are inconclusive because of the low statistical power of our study. We recommend a prospective study with a larger sample size that would increase the power and therefore the confidence in the results.

Background: The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART)., Methods: Lilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations., Results: Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158-361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). 'These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients<39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively]., Conclusions: Ocular inflammatory disease, mainly ocular tuberculosis, was common in a cohort of HIV/MDR-TB co-infected patients in Mumbai, India. Ophthalmological examination should be routinely considered in HIV patients diagnosed with or suspected to have MDR-TB, especially in those with extrapulmonary TB.

Background: Multidrug resistant (MDR) and extensively-drug resistant (XDR) tuberculosis (TB) are a serious threat to the national TB control programs of developing countries, and the situation is further worsened by the human immunodeficiency virus (HIV) pandemic. The literature regarding MDR/XDR-TB is, however, scanty from most parts of India. We carried out this study to assess the prevalence of MDR/XDR-TB in new and previously treated cases of pulmonary TB and in HIV seropositive and seronegative patients., Methods: Sputum and blood specimens were obtained from 2100 patients suspected of pulmonary tuberculosis and subjected to sputum microscopy and culture for TB, and HIV serology at our tertiary care centre in north India. The culture positive Mycobacterium tuberculosis isolates were subjected to drug susceptibility testing (DST) for first line anti-tuberculosis drugs, and the MDR isolates were further subjected to second line DST. Various parameters of the patients' were analyzed viz. clinical presentation, radiology, previous treatment history, demographic and socioeconomic data and microbiology results., Results: Of the 2100 patients, sputum specimens of 256 were smear positive for acid-fast bacilli (AFB), 271 (12.9%) grew Mycobacterium spp., and M. tuberculosis was isolated in 219 (10.42%). Of the 219 patients infected with M. tuberculosis, 20.1% (44/219) were found to be seropositive for HIV. Overall, MDR-TB was observed in 17.4% (39/219) isolates. There were 121 newly diagnosed and 98 previously treated patients, of which MDR-TB was found to be associated with 9.9% (12/121) and 27.6% (27/98) cases respectively. There was significantly higher association of MDR-TB (12/44, 27.3%) with HIV seropositive patients as compared to HIV seronegative patients (27/175, 15.4%) after controlling previous treatment status, age, and sex (odd's ratio, 2.3 [95% CI, 1.000-5.350]; p-value, 0.05). No XDR-TB was found among the MDR-TB isolates., Conclusion: The present study demonstrated a high prevalence of drug resistance amongst pulmonary TB isolates of M. tuberculosis from north India as compared to the WHO estimates for India in 2010, though this could possibly be attributed to the clustering of more serious or referred cases at our tertiary care centre. The prevalence of MDR-TB in HIV seropositive patients was significantly higher than seronegative individuals. The study emphasizes the need to monitor the trends of drug resistance in TB in various populations in order to timely implement appropriate interventions to curb the menace of MDR-TB.

Tuberculosis (TB) is responsible for a high mortality rate (2.5%) worldwide, mainly in developing countries with a high prevalence of human immunodeficiency virus (HIV). The emergence of multiresistant strains of TB poses an extreme risk for TB outbreaks and highlights the need for global TB control strategies. Among Western African countries, Côte d'Ivoire (CI) represents a specific example of a country with great potential to prevent TB. Specifically, CI has a promising healthcare system for monitoring diseases, including vaccination programs. However, military and political conflict in CI favors the spread of infectious diseases, TB being among the most devastating. Compilation of the studies identifying common causes of TB would be extremely beneficial for the development of treatment and prevention strategies. Therefore, the purpose of this comprehensive review is to evaluate the epidemiology of TB in CI, describe the factors involved in pathogenesis, and suggest simple and applicable prevention strategies.

Drug resistance is a major obstacle to effective TB control program performance. In this study, we assessed the prevalence of primary drug resistance in Mycobacterium tuberculosis (Mtb) isolates in Amhara Region, Ethiopia. A total of 112 Mtb isolates from cases with newly diagnosed pulmonary TB were subjected to drug susceptibility testing (DST) in a cross-sectional study. Isolates were tested for sensitivity to isoniazid, rifampicin, ethambutol, and streptomycin using the MGIT 960 protocol. A total of 93 Mtb isolates yielded valid DST results and 28 (30.1%) were resistant to one or more of first line anti-TB drugs. One isolate (1.0%) was multi-drug resistant (MDR), five (5.4%) were classified as poly-resistant and 22 showed single drug resistance to either streptomycin (n = 19) or isoniazid (n = 3). Isolates from HIV-positive patients were more likely to be resistant to at least one of the four anti-TB drugs compared with HIV-negative individuals (odds ratio 2.76, 95% confidence interval 1.06-7.22; p = 0.03). The study showed a high prevalence of primary drug resistance. Even though the prevalence of MDR was low, conditions that can contribute to the development of MDR are increasing. Therefore, regular monitoring of drug resistance and enhanced implementation of TB/HIV collaborative activities in the study region are imperative., (© 2012 The Authors. APMIS © 2012 APMIS.)

Drug-resistant tuberculosis (DR-TB) is an emerging global health threat as treatment involves complex multiple drug regimens, which are longer and more toxic than standard therapy and yet have worse outcomes. In the presence of resistance to one or more first-line drugs, an alternative regimen should be designed. A major problem is the almost complete lack of published evidence regarding the optimal drug combinations and duration of treatment for the different types of DR-TB. Current principles, some of which are based on expert opinion, are that at least three new anti-TB agents should be added to a failing regimen and four agents when multidrug resistance is suspected. All first-line oral anti-TB agents to which the Mycobacterium tuberculosis strains are susceptible should be used, plus one fluoroquinolone. In addition, one injectable anti-TB agent and one or more second-line oral anti-TB agents should be added to the regimen until the target number of drugs is reached. The duration of treatment depends on the type of drug resistance, the type and number of drugs used in the regimen, and the extent of the disease. All forms of DR-TB should receive daily, not intermittent, therapy and all doses should be directly observed. Because of the high rate of adverse drug effects, careful monitoring and appropriate management of these adverse reactions are important to achieve successful treatment. Supportive measures, such as adequate nutrition along with emotional and social supports, are an important part of the treatment. Careful consideration is required when dealing with pregnant or lactating women and HIV co-infected patients, as well as in treatment of extrapulmonary DR-TB., (© 2011 Adis Data Information BV. All rights reserved.)

Background: The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings., Methods: We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2-3 sputum smears and 1-3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used., Findings: We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0-1), compared with 1 day (0-1) for microscopy, 30 days (23-43) for solid culture, and 16 days (13-21) for liquid culture. Median time to detection of resistance was 20 days (10-26) for line-probe assay and 106 days (30-124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39-81) to 5 days (2-8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures., Interpretation: The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment., Funding: Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Tuberculosis (TB) coinfection with human immunodeficiency virus (HIV) is a substantial problem in South Africa. There has been a presumption that drug-resistant strains of TB are common in South Africa, but few studies have documented this impression., Methods: In Phidisa, a joint observational and randomized HIV treatment study for South African National Defence Force members and dependents, an initiative was launched to test subjects (by use of microbiologic TB test) who appeared to be at high risk. We report results for HIV-infected subjects., Results: TB was identified by culture in 116 (19.9%) of 584 patients selected for sputum examination on the basis of suggestive symptoms. Smear was an insensitive technique for confirming the diagnosis: only 33% of culture-positive patients were identified by smear, with a 0.2% false-positive rate. Of the 107 culture-positive individuals with susceptibility testing, 22 (20.6%) were identified to be multidrug resistant (MDR), and 4 (3.7%) were identified to be extensively drug resistant. Culture-positive cases with a history of TB treatment had more than twice the rate of MDR than those without (27.1% vs 11.9%; P = .05)., Conclusions: TB is common in this cohort of HIV-infected patients. Smear was not a sensitive technique for identifying culture-positive cases in this health system. Drug susceptibility testing is essential to proper patient management because MDR was present in 20.6% of culture-positive patients. Better management strategies are needed to reduce the development of MDR TB, because so many of these patients had received prior antituberculous therapy that was presumably not curative.

Background: The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in katG, rpoB and inhA genes, resulting in isoniazid (INH) and rifampin (RIF) resistance., Results: Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as M. bovis, 9 as M. avium and 1 as M. intracellulare. IS6110-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 M. bovis strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG --> TCG (Glu --> Ser) at codon 469 of rpoB gene., Conclusions: This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control.

The International Union Against Tuberculosis and Lung Disease/World Health Organization Global Project on Anti-Tuberculosis Drug Resistance Surveillance recently released the fourth global survey, which documents the highest burden of multidrug-resistant tuberculosis (TB) yet reported. The best estimate of the number of new cases of multidrug-resistant disease occurring in 2006 is close to half a million and the recent recognition of extensively drug-resistant TB underscores the need for expanded surveillance, especially in areas in which TB control programs have been compromised by an escalating burden of TB and HIV. We review current methods used for drug resistance surveillance and describe methodologic obstacles for estimating the true extent of the problem, particularly in settings where HIV/TB coinfection is common or where a substantial portion of TB cases are treated in the private sector. We highlight practical challenges to the validity of surveillance studies and discuss how additional investment in laboratory capacity, diagnostic technologies, and sentinel site surveillance can improve our ability to estimate of the burden of drug-resistant TB.

Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis have emerged as important infections in South Africa among patients infected with human immunodeficiency virus (HIV). In the face of this new epidemic, South Africa must rededicate itself to the task of tuberculosis control and treatment with a rapid, multifaceted approach. Priorities include expansion of second-line treatment capacity, investment in clinical laboratories, a system to ensure supervised treatment for all patients, and enhancement of infection control procedures. In New York City, where drug-resistant tuberculosis emerged 2 decades ago--also in the context of a large HIV-infected population and an underfunded public health infrastructure--similar steps were successful in leading to the rapid decrease in rates of drug resistance among tuberculosis isolates. With refinements based on local resource constraints, urgent measures could potentially arrest the alarming increase in multidrug-resistant and extensively drug-resistant tuberculosis cases in South Africa. Unlike many countries in sub-Saharan Africa, South Africa has the capacity to mount a rapid and large-scale response before drug-resistant tuberculosis envelops a much larger and far poorer region.

Drug-resistant tuberculosis (TB) is emerging as a major clinical and public health challenge in areas of sub-Saharan Africa where there is a high prevalence of human immunodeficiency virus (HIV) infection. TB drug-resistance surveillance in this region has been limited by laboratory capacity and the public health infrastructure; however, with the maturation of the HIV epidemic, the burden of drug-resistant TB is increasing rapidly. The recent discovery of large numbers of cases of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB in South Africa likely represents an unrecognized and evolving epidemic rather than sporadic, localized outbreaks. The combination of a large population of HIV-infected susceptible hosts with poor TB treatment success rates, a lack of airborne infection control, limited drug-resistance testing, and an overburdened MDR-TB treatment program provides ideal conditions for an MDR-TB and XDR-TB epidemic of unparalleled magnitude. In the present article, we review the history of drug-resistant TB in South Africa, describe its interaction with the HIV epidemic and the resultant consequences, and suggest measures necessary for controlling MDR-TB and XDR-TB in this context. A successful response to the emergence of MDR-TB and XDR-TB will necessitate increased resources for and collaboration between TB and HIV programs.

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative or of unknown HIV status (p<0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB.

The highest burden of human immunodeficiency virus (HIV) related tuberculosis (TB) is in sub-Saharan Africa. HIV complicates several areas of TB control, one of which involves treatment and treatment outcome. Large patient numbers cause congestion on TB wards, there is increased morbidity, an increased risk of adverse drug reactions, an increased case fatality, and an increased recurrence of TB after treatment completion. TB Control Programmes have responded to these problems by taking actions such as abolishing thioacetazone and decentralising the initial phase of treatment to peripheral health centres and the community. Despite this response, there are three major on-going concerns which need to be addressed by research studies. There is a need to reduce case fatality rates focusing on 1) stronger treatment regimens, 2) adequacy of rifampicin levels when intermittent treatment regimens are used, and 3) adjunctive treatments. There is a need to reduce recurrent rates of TB by 1) determining the relative role of re-infection and reactivation as a cause of recurrence, 2) assessing the importance of duration and type of anti-TB treatment for the first episode of TB, and 3) determining the role of secondary isoniazid preventive therapy. There is a need to evaluate how best to decentralise treatment from the perspective of the health service and the patient. Research studies should be relevant to the needs and resources of TB control programmes, and should include pharmacokinetic studies, controlled clinical trials and operational research, including economic analysis and social science evaluation.

Objective: To identify risk factors for transmission of multidrug-resistant tuberculosis (MDR-TB) among hospitalized human immunodeficiency virus (HIV) infected patients exposed during a nosocomial outbreak., Design: Case control study. Cases were HIV-infected patients with MDR-TB due to Mycobacterium bovis (MDR-TBMb) who acquired the disease after exposure to an MDR-TBMb patient in an hospital ward. Controls were HIV-infected patients exposed to a case of MDR-TBMb in an hospital ward but who did not develop MDR-TBMb during the follow-up., Results: Nineteen cases and 31 controls were included. CD4 cell counts were significantly lower among cases. Exposure in the infectious diseases ward or exposure to the index patient were associated with development of MDR-TBMb, while exposure during a single-room hospital stay and exposure in the respiratory isolation ward were associated with non-development of MDR-TBMb. A multiple regression logistic model showed that only a CD4 cell count below 50/microL and exposure to the index patient increased the risk of developing MDR-TBMb (P < 0.05). Hospitalization in a single room seemed to protect HIV-infected patients from developing nosocomial MDR-TBMb (P = 0.052)., Conclusions: Over classic risk factors, such as length of exposure or sharing a room with a case, severe immunosuppression independently increases the risk of MDR-TB transmission in the context of a nosocomial MDR-TB outbreak among HIV-infected patients. This information must be considered in the management of tuberculosis outbreaks. Patients with CD4 cell counts below 50/microL should be the principal group targeted for prevention strategies in nosocomial outbreaks.

Tuberculosis (TB) is the top killer of the productive age group in developing countries. More than half of cases in the world occur in Asia-Pacific region. The number of cases will increase in the next decades due to increase in urban poor population and HIV incidence, and poor access to health services and poor TB programme. The mainstay of effective strategy is to promote DOTS. DOTS population coverage is high, 58% in the Western Pacific Region but low; 29% in the southeast Asia region. Even among intermediate TB-burden countries in Asia, reduction of incidence has stagnated in recent years because of aging population, health problems in the urban poor population and influx of populations from high endemic areas. Indicators of successful TB programmes are high cure rate and low drug resistance rate. There is a strong correlation between the overall quality of TB control in the past and the current primary drug-resistant rate. To solve these problems, priority should be given to nationwide implementation of DOTS in high TB-burden countries with emphasis on ensuring availability of free anti-TB drugs and strengthening primary health care. General hospitals and private sector should be involved in control programmes to prevent drug resistant cases.

Tuberculosis (TB) was expected to be eradicated by the end of this century. However, an increasing incidence of tuberculosis in many parts of the world has led to renewed interest in the disease. The pandemic of HIV infection has changed TB, an endemic disease, to an epidemic worldwide. In Thailand, tuberculosis cases and deaths reduced year after year, until 1992 when the cases began to increase as a result of HIV infection. The annual risk of infection in 1997 was estimated at 1.4%, with approximately 100 000 new TB cases developing each year. Fifteen per cent of tuberculosis patients are seropositive for HIV infection. Increasing antituberculosis drug resistance has been correlated with the high prevalence of HIV infection in some parts of the country. In 1995, cure rate of this disease was approximately 50% and, since 1996, in order to cope with the worsening situation, the National Tuberculosis Programme (NTP) has adopted Directly Observed Treatment, Short-course (DOTS). Despite the current economic turmoil of the country, the programme has now been expanded to cover over 400 of the 810 districts of Thailand. Also, the economic effects of tuberculosis at the household level in Thailand were recently studied. Tuberculosis is a chronic disease that commonly affects the lower socioeconomic classes. Some patients were unable to follow the treatment regimens because of the financial burden. The low case detection and treatment completion rates are, in part, due to the inability of poor patients to cope with the expenditure.