Global TB Research Articles

Epidemiological Trends of Drug-Resistant Tuberculosis in China From 2007 to 2014: A Retrospective Study.

The emergence and spread of drug-resistant tuberculosis (DR-TB) has become the major concern in global TB control nowadays due to its limited therapy options and high mortality. A comprehensive evaluation for the epidemiological trends of DR-TB in mainland China, of which TB incidences remain high, is essential but lacking. This study aimed to describe the trends of DR-TB overtime, especially multidrug-resistant TB (MDR-TB); and to identify unique characteristics of MDR-TB cases compared with drug-susceptible TB cases in Mainland China.We retrospectively analyzed surveillance data collected from 36 TB prevention and control institutions in Shandong Province, China over an 8-year period. Unique characteristics of MDR-TB were identified; Chi-square test for trends and linear regression were used to assess the changes in proportions of different resistance patterns overtime.The overall MDR rate was 6.2% in our sample population. There were no statistically significant changes in the percentage of drug-susceptible, isoniazid (INH) resistance, ethambutol (EMB) resistance, streptomycin (SM) resistance, and MDR TB during our study period except that the overall rifampin (RFP) resistance and rifampin monoresistance (RMR) increased at a yearly rate of 0.2% and 0.1%, respectively. Among those with known treatment histories, a higher MDR rate of 8.7% was observed, in which 53.9% were primary MDR-TB patients, and this rate was increasing at a yearly rate of 4.1% over our study period. MDR-TB patients were more likely to be female (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.05–1.34), aged 25 to 44 years (OR, 1.67; 95%CI, 1.45–1.93), retreated (OR, 11.95; 95%CI, 9.68–14.76), having prior TB contact (OR, 1.89; 95%CI, 1.19–2.78) and having cavity (OR, 1.57; 95%CI 1.36–1.81), or bilateral disease (OR, 1.45; 95%CI 1.19–1.76) on chest radiology.Persistent high levels of MDR-TB, increasing rates of primary MDR-TB and RMR characterize DR-TB cases in mainland China; community-acquired drug resistance may be one of the most modifiable factors in future TB control strategies.

Epidemiology and Clinical Characteristics of Pediatric Drug-Resistant Tuberculosis in Chongqing, China.

To gain insight into the epidemiology of childhood drug resistant tuberculosis (DR-TB) in China that has the second largest burden of TB and the largest number of multidrug resistant (MDR) TB cases in the world, we performed the cross-sectional study to investigate drug resistance of four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) using Mycobacterium tuberculosis isolates from 196 culture-confirmed pediatric TB cases diagnosed in the Children’s Hospital of Chongqing Medical University, China during 2008–2013. Univariate and multivariate logistic regression analyses were performed to assess the associations between patient demographic and clinical characteristics and DR-and MDR-TB, respectively. Twenty-eight percent (56/196) of the study patients exhibited resistance to at least one of the four first-line anti-TB drugs tested. MDR was found in 4.6% (9/196) of the study patients. More than half (5/9, 55.6%) of the MDR cases were from a single county of Chongqing. A significant association was found between being acid-fast bacilli-smear negative and DR-TB (adjusted OR, 2.33; 95% CI, 1.13–4.80) and between having concurrent thoracic-extrathoracic involvement and MDR-TB (adjusted OR, 9.49; 95% CI, 1.05–85.92), respectively. The findings of this study indicate that the rate of DR is high among pediatric TB patients in Chongqing and suggest an urgent need for studies to identify MDR transmission hotspots in Chongqing, thereby contributing to the control DR- and MDR-TB epidemics in China. The study also generates new insight into the pathogenesis of DR and MDR M. tuberculosis strains and highlights the importance of studying childhood TB to the goal of global TB control.

Back to the future: Rethinking global control of tuberculosis.

If the ultimate goal of controlling an infectious disease is to interrupt transmission, the current global tuberculosis strategy is not succeeding.

Application of M&E System Strengthening Tool (MESST) to assess the M&E systems for HIV prevention and treatment programme in Sri Lanka

Introduction: Global Fund to fight AIDS, TB and Malaria (GFATM) is one of the main funding sources for Sri Lanka to achieve its national objectives on HIV prevention, treatment and care. The GFATM HIV/AIDS programme is collectively implemented by the National STD/AIDS Control Programme (NSACP) and non-government umbrella organizations (UOs). Grant recipients have to show results when requesting funds. Therefore, it is agreed that country HIV M&E systems should comply with the standard 12-components M&E system strengthening (MESS) tool. The objective of this assessment is to identify current strengths and weaknesses of the M&E systems and to develop a plan of action for system strengthening. Methods: MESS tool was used for the assessment which has 12 Excel worksheets to be completed by the M&E stakeholders in the NSACP and UOs. Three multidisciplinary groups (10 stakeholders per group) were formed and each was given 4 sheets to be completed by participatory approach. Worksheets have M&E related statements to be collectively graded by stakeholders considering the country context and M&E experiences. Results: MESS tool generate summary dashboards with regard to the collective grading of statements of the tool under 12-components. It showed both strengths and weaknesses in the prevailing M&E systems for HIV in the NSACP and UOs. Organization structure, human capacity, national and sub national databases as well as supportive supervision & auditing are main areas identified by the tool that need strengthening. Conclusions: MESS tool is an important organizing framework to identify strengths and weaknesses and gaps in the M&E system of the NSACP and UOs. Results reflect the areas to be strengthen and rectified in order to show realistic programme outcome and impact results. Sri Lanka Journal of Sexual Health and HIV Medicine Vol.1 2015: 7-11

The Lower Badenian transgressive-regressive cycles – a case study from Oslavany (Carpathian Foredeep, Czech Republic)

Two newly drilled boreholes (OSL-1 and OSL-2) at Oslavany (Carpathian Foredeep, Czech Republic, a holostratotype of the Moravian/Lower Badenian) provide data documenting the processes of the Lower Badenian marine transgression and regression along the passive margin of the peripheral foreland basin (south-eastern margin of the Bohemian Massif). Three facies associations show the evolution of the deposition and distinct basin margin paleogeography. Deposits of marine transgression (transgressive lag) are followed by open-marine (outer to inner shelf) deposits interpreted as transgressive and highstand systems tract. They reflect a cratonward shift of the coastline. The topmost foreshore and upper shoreface deposits (falling stage systems tract) recorded forced regression and basinward shift of the shoreline. The recorded transgressive-regressive cycle was induced by the coincidence of global TB 2.4. sea-level cycle and forebulge subsidence. The identified higher-frequency cycles were interpreted as climatically controlled.

Childhood TB: can the End TB Strategy deliver?

The accelerated reductions in global TB incidence required to achieve the End TB Strategy goal will result in reductions in the burden of childhood TB. Contact screening and preventive therapy have emerged as important components of TB burden reduction, and family-centered approaches could be an effective route in delivering these activities. Lack of accurate diagnostics for children remains a critical barrier and a need remains for better collaborative and supportive links between the child health and TB control sectors. Irrespective of whether the ambitious targets can be achieved, the unprecedented opportunities provided by the End TB Strategy must be embraced.

Management of multidrug-resistant TB: novel treatments and their expansion to low resource settings.

Despite overall progress in global TB control, the rising burden of multidrug-resistant TB (MDR-TB) threatens to undermine efforts to end the worldwide epidemic. Of the 27 countries classified as high burden for MDR-TB, 17 are in ‘low’ or ‘low–middle’ income countries. Shorter, all oral and less toxic multidrug combinations are required to improve treatment outcomes in these settings. Suitability for safe co-administration with HIV drugs is also desirable. A range of strategies and several new drugs (including bedaquiline, delamanid and linezolid) are currently undergoing advanced clinical evaluations to define their roles in achieving these aims. However, several clinical questions and logistical challenges need to be overcome before these new MDR-TB treatments fulfil their potential.

Drug-resistant TB: deadly, costly and in need of a vaccine.

TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associated with MDR-TB and XDR-TB, as the cost of treating disease caused by these strains can be 9–25 times higher than treating drug-susceptible TB. Developing new drugs, improved diagnostics and new TB vaccines are critical components of a strategy to combat TB in general, and drug-resistant TB in particular. Because Mycobacterium tuberculosis (MTB) has demonstrated a capacity to develop resistance to drugs developed to combat it, it is unlikely that drug-resistant MTB would be ‘resistant’ to vaccines capable of preventing disease or established infection with drug-sensitive MTB strains. Accordingly, the development of TB vaccines represents an important long-term investment in preventing the spread of drug-resistant TB and achieving WHO's goal of ending the global TB epidemic by 2035. Our current understanding of the epidemiology of drug-resistant TB and the interventions needed to limit its spread, reviewed in this article, illustrates the need for increased financial support for developing new TB drugs, diagnostics and vaccines to meet the WHO goal of TB elimination by 2035.

Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH): protocol for a multicentric prospective observational study

IntroductionTuberculosis disease (TB) remains an important global health threat. An evidence-based response, tailored to local disease epidemiology in high-burden countries, is key to controlling the global TB epidemic. Reliable surrogate...

Putting Guidelines into Practice: The Texas Children's Hospital Global TB Program's Experience with Multinational Clinical Monitoring and Evaluation

Putting Guidelines into Practice: The Texas Children's Hospital Global TB Program's Experience with Multinational Clinical Monitoring and Evaluation

Relationship between various social and demographic factors and its relation with treatment outcome in category II cases of tuberculosis in corporation area of Jamnagar, Gujarat, India

Background: Tuberculosis is a social disease with medical aspect. It has also been described as barometer of social welfare. India is the second-most populous country in the world. One fourth of the global incident TB cases occur in India annually. Various social and demographic factors are variably related to poor adherence. Methods: A longitudinal study was designed and all category II TB patients registered for DOTS treatment during period from July 2014 to December 2014 (2 Quarter), of corporation area in tuberculosis register of district TB centre were included in present study. Considering exclusion criteria total 89 patients were studied in present study. Results: Out of 89 patients mean age (+SD) of the patients were 38±16.1 years , 75.28% were male, 40.45% were labourers, 29.31% patients were illiterate, over all treatment success is 59 (66.29%). Out of 63 literate patients, 79.36% patients were successfully treated, while Among 26 illiterate patients, only 34.61% patients were successfully treated. Treatment outcome lower class (Modified B.G. Prasad classification class IV and class V) having only 53.70% treatment success rate. Conclusions: The findings of this study suggest that improvement in quality of life is necessary for better outcome. Future programme or research should focus on improvement of quality of life as well as reducing the duration of treatment for better compliance with.

Performance Characteristics of GenXpert MTB/rif in Armenia

Global TB control efforts have been severely hampered by the lack of diagnostic tests that are accurate, simple to use and can be applied at the point of clinical care. This has been further compounded by the widespread inability to test for drug resistance. We estimated the performance Characteristics of GenXpert MTB/rif of an active case finding program in Armenia where TB notifications is high. Armenia remains in the top ten out of the 27 high multidrug-resistant (MDR) TB burden countries in the world. According to the latest representative 2007 Drug Resistance Survey (DRS) 9.4% of new cases and 43.2% of previously treated cases were multi-drug resistant. Of these, 4% were extensively-drug-resistant tuberculosis (XDR/TB) cases. Detection of MDR-TB in Armenia remains at 37%. Despite of the fact that in 2013 all detected MDR-TB cases were enrolled in MDR-TB treatment, treatment success rate among 2011 MDR-TB cohort remains 51%, with 26% of patients defaulted therapy mostly due to labour migration, as the main reason of poor outcomes. Moreover, this can be accomplished using unprocessed sputum samples as well as clinical specimens from extrapulmonary sites. We review the development of this assay, its evaluation within the laboratory, its utility among adult and pediatric TB suspects, its use as a screening tool for HIV-associated TB and studies of its implementation at the central level. The Xpert® MTB/RIF assay is a rapid molecular assay that can be used close to the point of care by operators with minimal technical expertise, enabling diagnosis of TB and simultaneous assessment of rifampicin resistance to be completed within 2 h.

Tuberculosis: the current status in India

Pulmonary tuberculosis is endemic globally and is responsible for considerable morbidity and mortality. India is classified among the 22 high burden countries by WHO. According to WHO global TB report 2015 incidence of TB in India in 2014 was 2.2 million (including patients with HIV/TB) while, prevalence was 2.5 million (includes patients with HIV/TB). Mortality (excluding patients wit HIV/TB) was 0.2 million and case detection for all forms of TB was approximately 74%. With the emerging threat of Drug-Resistant TB, We need to improve our surveillance and treatment facility to eliminate TB by 2050. Key words: Pulmonary tuberculosis, HIV/ TB

Inhaled drug treatment for tuberculosis: Past progress and future prospects

Since the 1990s the rising incidence of multiple drug resistant TB, particularly in the context of human immunodeficiency virus co-infected patients, has threatened global TB control. At that time funding agencies began to support formal investigation of aerosol therapy which until then had been the subject of case reports of individual investigators. Over the last decade, proponents of aerosol therapy have increased in number within the TB research community as the incidence of multiple and extremely drug resistant TB has increased dramatically around the world. Aerosol therapy offers the potential to deliver drug at target concentrations directly into the lungs, use the alveolar-capillary interface to achieve systemic levels, while reducing the risk of systemic toxicity seen with parentally administered doses. In addition, there are insufficient new drugs in the pipeline to anticipate the appearance of a new regimen in time to assure future control of drug resistance. Consequently, alternative strategies are critical to achieving global TB control, and inhaled therapies should be considered as one such strategy.

First-in-Class Inhibitors of Sulfur Metabolism with Bactericidal Activity against Non-Replicating M. tuberculosis.

Development of effective therapies to eradicate persistent, slowly replicating M. tuberculosis (Mtb) represents a significant challenge to controlling the global TB epidemic. To develop such therapies, it is imperative to translate information from metabolome and proteome adaptations of persistent Mtb into the drug discovery screening platforms. To this end, reductive sulfur metabolism is genetically and pharmacologically implicated in survival, pathogenesis, and redox homeostasis of persistent Mtb. Therefore, inhibitors of this pathway are expected to serve as powerful tools in its preclinical and clinical validation as a therapeutic target for eradicating persisters. Here, we establish a first functional HTS platform for identification of APS reductase (APSR) inhibitors, a critical enzyme in the assimilation of sulfate for the biosynthesis of cysteine and other essential sulfur-containing molecules. Our HTS campaign involving 38 350 compounds led to the discovery of three distinct structural classes of APSR inhibitors. A class of bioactive compounds with known pharmacology displayed potent bactericidal activity in wild-type Mtb as well as MDR and XDR clinical isolates. Top compounds showed markedly diminished potency in a conditional ΔAPSR mutant, which could be restored by complementation with Mtb APSR. Furthermore, ITC studies on representative compounds provided evidence for direct engagement of the APSR target. Finally, potent APSR inhibitors significantly decreased the cellular levels of key reduced sulfur-containing metabolites and also induced an oxidative shift in mycothiol redox potential of live Mtb, thus providing functional validation of our screening data. In summary, we have identified first-in-class inhibitors of APSR that can serve as molecular probes in unraveling the links between Mtb persistence, antibiotic tolerance, and sulfate assimilation, in addition to their potential therapeutic value.

Early culture conversion and cure for extensively drug-resistant tuberculosis is possible with appropriate treatment: lessons learnt from a case study in South Africa.

Despite the relevance of extensively drug-resistant tuberculosis (XDR-TB) to global TB control efforts, case reports on patients achieving cure are scarce. The case of a patient who was treated for more than 3 years as a multidrug-resistant TB (MDR-TB) case, and who was diagnosed retrospectively with XDR-TB, is presented herein. Soon after the initiation of a capreomycin and para-aminosalicylic acid-based regimen, the patient converted and treatment was completed successfully.

Moving Beyond Directly Observed Therapy for Tuberculosis.

Moving Beyond Directly Observed Therapy for Tuberculosis.

Designing and implementing a socioeconomic intervention to enhance TB control: operational evidence from the CRESIPT project in Peru.

BackgroundCash transfers are key interventions in the World Health Organisation’s post-2015 global TB policy. However, evidence guiding TB-specific cash transfer implementation is limited. We designed, implemented and refined a novel TB-specific socioeconomic intervention that included cash transfers, which aimed to support TB prevention and cure in resource-constrained shantytowns in Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.MethodsNewly-diagnosed TB patients from study-site healthposts were eligible to receive the intervention consisting of economic and social support. Economic support was provided to patient households through cash transfers on meeting the following conditions: screening for TB in household contacts and MDR TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social support (household visits and community meetings).To evaluate project acceptability, quantitative and qualitative feedback was collected using a mixed-methods approach during formative activities. Formative activities included consultations, focus group discussions and questionnaires conducted with the project team, project participants, civil society and stakeholders.ResultsOver 7 months, 135 randomly-selected patients and their 647 household contacts were recruited from 32 impoverished shantytown communities. Of 1299 potential cash transfers, 964 (74 %) were achieved, 259 (19 %) were not achieved, and 76 (7 %) were yet to be achieved. Of those achieved, 885/964 (92 %) were achieved optimally and 79/964 (8 %) sub-optimally.Key project successes were identified during 135 formative activities and included: strong multi-sectorial collaboration; generation of new evidence for TB-specific cash transfer; and the project being perceived as patient-centred and empowering.Challenges included: participant confidence being eroded through cash transfer delays, hidden account-charges and stigma; access to the initial bank-provider being limited; and conditions requiring participation of all TB-affected household members (e.g. community meetings) being hard to achieve.Refinements were made to improve project acceptability and future impact: the initial bank-provider was changed; conditional and unconditional cash transfers were combined; cash transfer sums were increased to a locally-appropriate, evidence-based amount; and cash transfer size varied according to patient household size to maximally reduce mitigation of TB-related costs and be more responsive to household needs.ConclusionsA novel TB-specific socioeconomic intervention including conditional cash transfers has been designed, implemented, refined and is ready for impact assessment, including by the CRESIPT project. The lessons learnt during this research will inform policy-makers and decision-makers for future implementation of related interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2128-0) contains supplementary material, which is available to authorized users.

Prevalence and drug resistance profile of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients attending two public hospitals in East Gojjam zone, northwest Ethiopia.

BackgroundThe spread of multidrug-resistant tuberculosis (MDR-TB) strains has become a challenge to the global TB control and prevention program. In Ethiopia, particularly in rural areas, information on drug-resistant TB is very limited. In this study, we determined the drug resistance patterns of Mycobacterium tuberculosis (M. tuberculosis) isolates from pulmonary TB patients attending two public hospitals in the East Gojjam zone of northwest Ethiopia.MethodsA cross-sectional study was conducted between May 2011 and January 2012 using Region of difference-9 (RD9) typing for the identification of species mycobacterium. Drug susceptibility testing (DST) of M. tuberculosis isolates to the first-line drugs: isoniazid, rifampicin, ethambutol and streptomycin was performed by the indirect proportion method on Middle brook 7H10 Agar media.ResultsOut of 385 pulmonary TB suspects studied, 124 (32.2 %) were culture positive among which 120 were M. tuberculosis strains. Susceptibility testing was performed for 89 isolates. Resistance to at least one drug was 15.58 % ([12/77], 95 % CI: 7.48-23.68) among newly diagnosed and 50.0 % ([6/12], 95 % CI: 21.71-78.29) among previously treated cases. Resistance among newly diagnosed patients was most common for streptomycin 5.19 % (4/77) and ethambutol 5.19 % (4/77) followed by rifampicin 3.89 % (3/77). Among retreatment cases, isoniazid resistance was most frequent in which 33.33 % (4/12) of the isolates were resistant. MDR prevalence was 1.29 % (1/77) for newly diagnosed and 16.67 % (2/12) for retreatment cases. In a multivariate logistic regression analysis, age group of 25–34 years (adjusted OR = 4.24; 95 % CI: 1.02-17.5; P = 0.046) and previous history of treatment (adjusted OR = 5.42; 95 % CI: 1.56-27.49; P = 0.01) were independently associated with anti-TB drug resistance.ConclusionsIn general, the magnitude of anti-TB drug resistance including MDR-TB was comparable to previous studies in other areas of Ethiopia. However, rifampicin resistance was high, which could suggest the potential for a rise in the incidence of MDR. Therefore, re-enforcing TB control programs should be considered by the concerned public health authorities.

Editorial introductions

Editorial introductions