Population-wide active case finding as a strategy to end TB.

Tuberculosis (TB) is the leading infectious cause of morbidity and mortality globally. Despite available tools for preventing, finding, and treating TB, many people with TB remain undiagnosed. In high-incidence settings, TB transmission is ubiquitous within the community, affecting both high-risk groups and the general population.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to () transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare.

Methods: We reviewed the literature to identify studies where surveys of infection were linked to population surveys of TB disease.

Standards for clinical trials for treating TB.

The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice. A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached. Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.

Progress on diagnosis and treatment of drug-resistant tuberculosis in line with World Health Organization recommendations in six priority countries in the Western Pacific Region.

Background: Diagnosis and treatment of drug-resistant tuberculosis (DR-TB) have radically changed in accordance with recommendations from the World Health Organization (WHO) in the past decade, allowing rapid and simple diagnosis and shorter treatment duration with new and repurposed drugs.

Methods: A descriptive analysis of the status and progress of DR-TB diagnosis and treatment in six priority countries in the Western Pacific Region was conducted using information from interviews with countries and the WHO TB database.

Results: Over the past decade, the use of Xpert MTB/RIF has increased in the six priority countries, in parallel with implementation of national policies and algorithms to use Xpert MTB/RIF as an initial diagnostic test for TB and detection of rifampicin resistance.

High Levels of Treatment Success and Zero Relapse in Multidrug-Resistant Tuberculosis Patients Receiving a Levofloxacin-Based Shorter Treatment Regimen in Vietnam.

Vietnam has been using a levofloxacin-based shorter treatment regimen (STR) for rifampicin resistant/multidrug-resistant tuberculosis (RR/MDR-TB) patients since 2016 on a pilot basis. This regimen lasts for 9-11 months and is provided to RR/MDR-TB patients without second-line drug resistance. We report the treatment outcomes and factors associated with unsuccessful outcomes.

Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences.

New drugs and shorter treatments for drug-resistant tuberculosis (DR-TB) have become available in recent years and active pharmacovigilance (PV) is recommended by the World Health Organization (WHO) at least during the early phases of implementation, with active drug safety monitoring and management (aDSM) proposed for this. We conducted a literature review of papers reporting on aDSM. Up to 18 April, 2019, results have only been published from one national aDSM programme.

Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method.

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

Background: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis.

Genotypic characteristics of Mycobacterium tuberculosis isolated from household contacts of tuberculosis patients in the Philippines.

Background: The Philippines has an extremely high rate of tuberculosis but little is known about M. tuberculosis genotypes and transmission dynamics in this country. The aim of this study was to determine the proportion of household contacts who develop active TB due to direct transmission from an index case in that household.

Patterns of treatment interruption among patients with multidrug-resistant TB (MDR TB) and association with interim and final treatment outcomes.

Background: The reasons that patients with multidrug-resistant tuberculosis (MDR TB) miss treatment are multi-factorial and complex. Identifying patterns of treatment interruption that predict poor outcomes can be used to target program activities aiming to improve treatment adherence.

Objective: To characterize patterns of treatment interruption among MDR TB patients and determine the association between patterns and treatment outcomes.

Predictors of sputum culture conversion among patients treated for multidrug-resistant tuberculosis.

Objective: To identify predictors of initial sputum culture conversion, estimate the usefulness of persistent positive cultures at different time points in predicting treatment failure, and evaluate different definitions of culture conversion for predicting failure among patients with multidrug-resistant tuberculosis (MDR-TB) in five countries, 2000-2004.

Methods: Predictors of time to conversion were identified using multivariate Cox proportional hazards regression modeling. Receiver operating characteristic curves were plotted to visualize the effect of using different definitions of 'culture conversion' on the balance between sensitivity and specificity.

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.

Methods And Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB.

Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects.

The Objective of this analysis was to identify predictors of death, failure, and default among MDR-TB patients treated with second-line drugs in DOTS-plus projects in Estonia, Latvia, Philippines, Russia, and Peru, 2000-2004. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using multivariable regression. Of 1768 patients, treatment outcomes were: cure/completed - 1156 (65%), died - 200 (11%), default - 241 (14%), failure - 118 (7%).

Impact of patient and program factors on default during treatment of multidrug-resistant tuberculosis.

Setting: In the Philippines, programmatic treatment of drug-resistant tuberculosis (TB) was initiated by the Tropical Disease Foundation in 1999 and transitioned to the National TB Program in 2006.

Objective: To determine patient and socio-demographic characteristics associated with default, and the impact of patient support measures on default.

Design: Retrospective cohort analysis of 583 MDR-TB patients treated from 1999 to 2006.

Bacteriologic monitoring of multidrug-resistant tuberculosis patients in five DOTS-Plus pilot projects.

Background: Multidrug-resistant tuberculosis programs in DOTS-Plus pilot sites in five countries.

Objectives: To calculate sputum conversion time and its relationship to treatment outcome, document the frequency of culture reversions and examine concordance of smear and culture to assess the potential consequences of monitoring by smear microscopy alone.

Design: Retrospective cohort analysis of 1926 patients receiving individualized, second-line therapy.

Frequency and type of microbiological monitoring of multidrug-resistant tuberculosis treatment.

Monthly culture is usually recommended to monitor treatment of multidrug-resistant tuberculosis (MDR-TB). As mycobacterial laboratory capacity is limited in many settings, TB programs need evidence to decide whether monthly cultures are necessary compared to other approaches. We simulated three alternative monitoring strategies (culture every 2 or 3 months, and monthly smears alone) in a cohort of MDR-TB patients in Estonia, Latvia, Philippines, Russia and Peru from 2000 to 2004.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations.

Clinical symptoms and microbiological outcomes in tuberculosis treatment trials.

During a recent Food and Drug Administration workshop on clinical trials to evaluate new TB drugs, questions were raised regarding the use of bacteriologic endpoints such as treatment failure and relapse as measures of improvement in health status and long term outcome after treatment. FDA scientists asked how patients' clinical signs and symptoms changed during therapy, noting that while such information is usually collected during clinical trials, it is not often reported. We analyzed data from an international phase 3 TB treatment trial that included systematic assessments of symptoms.

Multidrug-resistant tuberculosis among previously treated patients in the Philippines.

Setting: Prior treatment has been associated with multidrug-resistant tuberculosis (MDR-TB) in many settings. The Philippines ranks fifth among 27 priority countries for MDR-TB.

Objective: To determine the rate of MDR-TB among previously treated patients referred for MDR screening and management.

Responding to the multidrug-resistant tuberculosis crisis: mainstreaming programmatic management to the Philippine National Tuberculosis Programme.

Setting: The Philippines ranks eighth among 27 priority countries for multidrug-resistant TB (MDR-TB).

Objective: To describe a model of public-private partnership in MDR-TB management.

Methods: An exploratory study of integrating MDR-TB management initiated in private-public mix DOTS into the National TB Programme (NTP).

Significant decline in the tuberculosis burden in the Philippines ten years after initiating DOTS.

Background: The Philippines ranks ninth among the 22 high-burden countries for tuberculosis (TB).

Objective: To measure the burden of pulmonary tuberculosis (PTB) in the Philippines and determine the impact of the DOTS strategy.

Materials And Methods: The 2007 nationwide TB prevalence survey covered 50 clusters selected by multi-stage stratified random sampling from Metro Manila and other urban and rural areas.

Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion.

Rationale: Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients.

Objectives: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months.

Feasibility and cost-effectiveness of treating multidrug-resistant tuberculosis: a cohort study in the Philippines.

Background: Multidrug-resistant tuberculosis (MDR-TB) is an important global health problem, and a control strategy known as DOTS-Plus has existed since 1999. However, evidence regarding the feasibility, effectiveness, cost, and cost-effectiveness of DOTS-Plus is still limited.

Methodology/principal Findings: We evaluated the feasibility, effectiveness, cost, and cost-effectiveness of a DOTS-Plus pilot project established at Makati Medical Center in Manila, the Philippines, in 1999.