Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible brain proteinopathy. Five main clinicopathological subtypes (sCJD-MM(V)1, -MM(V)2C, -MV2K, -VV1, and -VV2) are currently distinguished. Histopathological evidence suggests that the localisation of prion aggregates and spongiform lesions varies among subtypes. Establishing whether there is an initial site with detectable imaging abnormalities (epicentre) and an order of lesion propagation would be informative for disease early diagnosis, patient staging, management and recruitment in clinical trials. Diffusion magnetic resonance imaging (MRI) is the most-used and most-sensitive test to detect spongiform degeneration. This study was designed to identify, in vivo and for the first time, subtype-dependent epicentre and lesion propagation in the brain using diffusion-weighted images (DWI), in the largest known cross-sectional dataset of autopsy-proven subjects with sCJD. We estimate lesion propagation by cross-sectional DWI using event-based modelling, a well-established data-driven technique. DWI abnormalities of 594 autopsy-diagnosed subjects (448 patients with sCJD) were scored in 12 brain regions by 1 neuroradiologist blind to the diagnosis. We used the event-based model to reconstruct sequential orderings of lesion propagation in each of five pure subtypes. Follow-up data from 151 patients validated the estimated sequences. Results showed that epicentre and ordering of lesion propagation are subtype specific. The two most common subtypes (-MM1 and -VV2) showed opposite ordering of DWI abnormality appearance: from the neocortex to subcortical regions, and vice versa, respectively. The precuneus was the most likely epicentre also in -MM2 and -VV1 although at variance with -MM1, abnormal signal was also detected early in cingulate and insular cortices. The caudal-rostral sequence of lesion propagation that characterises -VV2 was replicated in -MV2K. Combined, these data-driven models provide unprecedented dynamic insights into subtype-specific epicentre at onset and propagation of the pathologic process, which may also enhance early diagnosis and enable disease staging in sCJD.

The incidence of tuberculosis (TB) disease in the United States has stabilized, and additional interventions are needed to make progress toward TB elimination. But the impact of such interventions depends on local demography and heterogeneity in populations at risk. Using state-level individual-based TB transmission models, calibrated to California, Florida, New York, and Texas, we modeled two TB interventions: (i) Increased targeted testing and treatment (TTT) of high-risk populations, including people who are non-US-born, diabetic, HIV-positive, homeless, or incarcerated; and (ii) Enhanced TB contact investigation (ECI), including higher completion of preventive therapy. For each intervention, we projected reductions in active TB incidence over 10 years (2016-2026) and numbers needed to screen and treat to avert one case. TTT delivered to half of the non-US-born adult population could lower TB incidence by 19.8%-26.7% over ten years. TTT delivered to smaller populations with higher TB risk (e.g., HIV-positive, homeless) and ECI were generally more efficient, but had less overall impact on incidence. TTT targeted to smaller, highest-risk populations, and ECI can be highly efficient; however, major reductions in incidence will only be achieved by also targeting larger, moderate-risk populations. Ultimately, to eliminate TB in the US, a combination of these approaches is necessary.

The current tuberculosis (TB) case reporting system for the United States, the Report of Verified Case of TB (RVCT), has minimal capture of multidrug-resistant (MDR) TB treatment and adverse events. Data were abstracted in five states using the form for 13 MDR TB patients during 2012–2015. The Centers for Disease Control and Prevention Guidelines for Evaluating Public Health Surveillance Systems were used to evaluate attributes of the form. Unstructured interviews with pilot sites and stakeholders provided qualitative feedback. The form was acceptable, simple, stable, representative, and provided high-quality data but was not flexible or timely. For the 13 patients on whom data were collected, the median duration of treatment with an injectable medication was 216 days (IQR 203–252). Six (46%) patients reported a side effect requiring a medication change and eight (62%) had a side effect present at treatment completion. A standardized MDR TB supplemental surveillance form was well received by stakeholders whose feedback was critical to making modifications. The finalized form will be implemented nationally in 2020 and will provide MDR TB treatment and morbidity data in the United States to help ensure patients with MDR TB receive the most effective treatment regimens with the least toxic drugs.

Tuberculosis (TB) is the leading infectious disease cause of death worldwide, yet many persons in industrialized countries think TB is mainly a historical curiosity or a rare disease only affecting a few uniquely vulnerable persons. This paradox is the inspiration for Kathryn Lougheed’s book, Catching Breath: The Making and Unmaking of Tuberculosis (Figure). After spending a decade at the bench exploring the mycobacterium as a microbiologist, the author embraced broader historical questions and embarked on a personal pilgrimage, as if learning about the disease for the first time. The result is, in her own words, a “whistle-stop tour through the past few million years to pick apart what has made TB ‘TB’.”