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Background International guidelines recommend monitoring weight as an indicator of therapeutic response in childhood tuberculosis (TB) disease. This recommendation is based on observations in adults. In the current study, we evaluated the association between weight change and treatment outcome, the accuracy of using weight change to predict regimen efficacy, and whether successfully treated children achieve catch-up weight gain. Methods We enrolled children treated for drug-susceptible TB disease (group 1) and multidrug-resistant TB disease (group 2) in Peru. We calculated the change in weight-for-age z score (ΔWAZ) between baseline and the end of treatment months 2–5 for group 1, and between baseline and months 2–8 for group 2. We used logistic regression and generalized estimating equation models to evaluate the relationship between ΔWAZ and outcome. We plotted receiver operating characteristic curves to determine the accuracy of ΔWAZ for predicting treatment failure or death. Results Groups 1 and 2 included 100 and 94 children, respectively. In logistic regression, lower ΔWAZ in months 3–5 and month 7 was associated with treatment failure or death in groups 1 and 2, respectively. In generalized estimating equation models, children in both groups who experienced treatment failure or death had lower ΔWAZ than successfully treated children. The ΔWAZ predicted treatment failure or death with 60%–90% sensitivity and 60%–86% specificity in months 2–5 for group 1 and months 7–8 for group 2. All successfully treated children—except group 2 participants with unknown microbiologic confirmation status—achieved catch-up weight gain. Conclusions Weight change early in therapy can predict the outcome of childhood TB treatment. [ABSTRACT FROM AUTHOR]

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Tuberculosis (TB) is an airborne infectious disease that is both preventable and curable, yet it kills more than a million people every year. Children are highly vulnerable, but often invisible casualties. Drug-resistant forms of TB are on the rise globally, and children are as vulnerable as adults but less likely to be counted as cases of drug-resistant disease if they become sick. Four factors make children with drug-resistant TB 'invisible': first, the nature of the disease in children; second, deficiencies in existing diagnostic tools; third, overreliance on these tools; and fourth, our collective failure to deploy one effective tool for finding and treating children - contact investigation. We describe a nascent science-advocacy network - the Sentinel Project on Pediatric Drug-Resistant Tuberculosis - whose goal is to end child deaths from this disease. Provisional annual targets, focused on children exposed at home to multidrug-resistant TB, to be updated every year, constitute a framework to focus attention and collective actions at the community, national, and global levels. The targets in two age groups, under 5 and 5-14 years old, tell us the number of: (i) children who require complete evaluation for TB disease and infection; (ii) children who require treatment for TB disease; and (iii) children who would benefit from preventive therapy. [ABSTRACT FROM AUTHOR]

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs. [ABSTRACT FROM AUTHOR]

In an extensively previously treated patient population, receipt of an aggressive regimen (ie, one containing ≥5 likely effective drugs, including a fluoroquinolone and injectable) for ≥18 months following sputum conversion, was associated with a reduced risk of recurrence.Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy.Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis.Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2–53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17–0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17–50.60]; P = .004).Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease. [ABSTRACT FROM PUBLISHER]

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. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). Conclusions: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. [ABSTRACT FROM AUTHOR]

We estimated the proportion of recurrence within 2 years among adults cured by individualized multidrug-resistant tuberculosis regimens in Peru. Among 310 individuals with at least 24 months of follow-up, 16 experienced an episode of recurrent tuberculosis. If we assume the worst for treatment effectiveness—that all 16 episodes were caused by the original tuberculosis strain—then 5.2% (95% confidence interval, 3.0%-8.2%) experienced true relapse. This is an upper-bound estimate of relapse on which new regimens must improve. [ABSTRACT FROM AUTHOR]

Focuses on the resurgence of tuberculosis (TB) in post-Soviet Tajikistan as an instance of structural violence. Definition of structural violence; Effect of the collapse of the Soviet state on the impoverished Tajikistan; Accompanying transition in subsidized health care; Effect on treatment of TB in Tajikistan.

Background: Case fatality ratios in children with tuberculosis are poorly understood-particularly those among children with HIV and children not receiving tuberculosis treatment. We did a systematic review of published work to identify studies of population-representative samples of paediatric (ie, <15 years) tuberculosis cases.Methods: We searched PubMed and Embase for reports published in English, French, Portuguese, or Spanish before Aug 12, 2016, that included terms related to tuberculosis, children, mortality, and population representativeness. We also reviewed our own files and reference lists of articles identified by this search. We screened titles and abstracts for inclusion, excluding studies in which outcomes were unknown for 10% or more of the children and publications detailing non-representative samples. We used random-effects meta-analysis to produce pooled estimates of case fatality ratios from the included studies, which we divided into three eras: the pre-treatment era (ie, studies before 1946), the middle era (1946-80), and the recent era (after 1980). We stratified our analyses by whether or not children received tuberculosis treatment, age (0-4 years, 5-14 years), and HIV status.Findings: We identified 31 papers comprising 35 datasets representing 82 436 children with tuberculosis disease, of whom 9274 died. Among children with tuberculosis included in studies in the pre-treatment era, the pooled case fatality ratio was 21·9% (95% CI 18·1-26·4) overall. The pooled case fatality ratio was significantly higher in children aged 0-4 years (43·6%, 95% CI 36·8-50·6) than in those aged 5-14 years (14·9%, 11·5-19·1). In studies in the recent era, when most children had tuberculosis treatment, the pooled case fatality ratio was 0·9% (95% CI 0·5-1·6). US surveillance data suggest that the case fatality ratio is substantially higher in children with HIV receiving treatment for tuberculosis (especially without antiretroviral therapy) than in those without HIV.Interpretation: Without adequate treatment, children with tuberculosis, especially those younger than 5 years, are at high risk of death. Children with HIV have an increased mortality risk, even when receiving tuberculosis treatment.Funding: US National Institutes of Health, Janssen Global Public Health. [ABSTRACT FROM AUTHOR]

Summary: Background: In many countries with a high burden of tuberculosis, most patients receive treatment in the private sector. We evaluated a multifaceted case-detection strategy in Karachi, Pakistan, targeting the private sector. Methods: A year-long communications campaign advised people with 2 weeks or more of productive cough to seek care at one of 54 private family medical clinics or a private hospital that was also a national tuberculosis programme (NTP) reporting centre. Community laypeople participated as screeners, using an interactive algorithm on mobile phones to assess patients and visitors in family-clinic waiting areas and the hospital''s outpatient department. Screeners received cash incentives for case detection. Patients with suspected tuberculosis also came directly to the hospital''s tuberculosis clinic (self-referrals) or were referred there (referrals). The primary outcome was the change (from 2010 to 2011) in tuberculosis notifications to the NTP in the intervention area compared with that in an adjacent control area. Findings: Screeners assessed 388 196 individuals at family clinics and 81 700 at Indus Hospital''s outpatient department from January–December, 2011. A total of 2416 tuberculosis cases were detected and notified via the NTP reporting centre at Indus Hospital: 603 through family clinics, 273 through the outpatient department, 1020 from self-referrals, and 520 from referrals. In the intervention area overall, tuberculosis case notification to the NTP increased two times (from 1569 to 3140 cases) from 2010 to 2011—a 2·21 times increase (95% CI 1·93–2·53) relative to the change in number of case notifications in the control area. From 2010 to 2011, pulmonary tuberculosis notifications at Indus Hospital increased by 3·77 times for adults and 7·32 times for children. Interpretation: Novel approaches to tuberculosis case-finding involving the private sector and using laypeople, mobile phone software and incentives, and communication campaigns can substantially increase case notification in dense urban settings. Funding: TB REACH, Stop TB Partnership. [Copyright &y& Elsevier]