Building a tuberculosis-free world: The Lancet Commission on tuberculosis

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer

Seven challenges in modelling pathogen dynamics within-host and across scales

The population dynamics of infectious disease is a mature field in terms of theory and to some extent, application. However for microparasites, the theory and application of models of the dynamics within a single infected host is still an open field. Further, connecting across the scales – from cellular to host level, to population level – has potential to vastly improve our understanding of pathogen dynamics and evolution. Here, we highlight seven challenges in the following areas: transmission bottlenecks, heterogeneity within host, dynamic fitness landscapes within hosts, making use of next-generation sequencing data, capturing superinfection and when and how to model more than two scales

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefol

Geographical location of study treatment units and the demographic classification assigned to each project treatment unit site.

<p>Geographical location of study treatment units and the demographic classification assigned to each project treatment unit site.</p

Enrollment of presumptive tuberculosis and drug resistant tuberculosis cases in baseline and intervention period of the study.

<p>Enrollment of presumptive tuberculosis and drug resistant tuberculosis cases in baseline and intervention period of the study.</p

Characteristics of persons tested for pulmonary tuberculosis by study phase, at the 14 study treatment units with data collection both in the baseline and intervention phase.

<p>Abbreviations: ART = antiretroviral treatment; NGO = non-governmental organization; PTB = pulmonary tuberculosis; Bacteriologically confirmed PTB = All bacteriologically diagnosed (smear and or Xpert MTB/RIF) PTB cases; sm = sputum smear microscopy; Xp = Xpert MTB/RIF; neg = negative; pos = positive; na = not available</p><p>Characteristics of persons tested for pulmonary tuberculosis by study phase, at the 14 study treatment units with data collection both in the baseline and intervention phase.</p