Molecular Imaging of Tuberculosis

Background The existing estimate of the global burden of latent TB infection (LTBI) as “one-third” of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. Methods and Findings We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%–26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%–0.9%) of the global population, amounting to 55.5 (95% UI: 48.2–63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%–11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI. Conclusions We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached.

The recent development of quinoline-based PET tracers that act as fibroblast-activation-protein inhibitors (FAPIs) demonstrated promising preclinical and clinical results. FAP is overexpressed by cancer-associated fibroblasts of several tumor entities. Here, we quantify the tumor uptake on 68Ga-FAPI PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods:68Ga-FAPI PET/CT scans were requested by various referring physicians according to individual clinical indications that were considered insufficiently covered by 18F-FDG PET/CT or other imaging modalities. All PET/CT was performed 1 h after injection of 122-312 MBq of 68Ga-FAPI-04. We retrospectively identified 80 patients with histopathologically proven primary tumors or metastases or radiologically unequivocal metastatic lesions of histologically proven primary tumors. Tumor uptake was quantified by SUVmax and SUVmean (60% isocontour). Results: Eighty patients with 28 different tumor entities (54 primary tumors and 229 metastases) were evaluated. The highest average SUVmax (>12) was found in sarcoma, esophageal, breast, cholangiocarcinoma, and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax < 6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic, and gastric cancer. The average SUVmax of hepatocellular, colorectal, head-neck, ovarian, pancreatic, and prostate cancer was intermediate (SUV 6-12). SUV varied across and within all tumor entities. Because of low background in muscle and blood pool (SUVmax < 2), the tumor-to-background contrast ratios were more than 3-fold in the intermediate and more than 6-fold in the high-intensity uptake group. Conclusion: Several highly prevalent cancers presented with remarkably high uptake and image contrast on 68Ga-FAPI PET/CT. The high and rather selective tumor uptake may open up new applications for noninvasive tumor characterization, staging examinations, or radioligand therapy.

The main thrust of the World Health Organization's global tuberculosis (TB) control strategy is to ensure effective and equitable delivery of quality assured diagnosis and treatment of TB. Options for including preventive efforts have not yet been fully considered. This paper presents a narrative review of the historical and recent progress in TB control and the role of TB risk factors and social determinants. The review was conducted with a view to assess the prospects of effectively controlling TB under the current strategy, and the potential to increase epidemiological impact through additional preventive interventions. The review suggests that, while the current strategy is effective in curing patients and saving lives, the epidemiological impact has so far been less than predicted. In order to reach long-term epidemiological targets for global TB control, additional interventions to reduce peoples' vulnerability for TB may therefore be required. Risk factors that seem to be of importance at the population level include poor living and working conditions associated with high risk of TB transmission, and factors that impair the host's defence against TB infection and disease, such as HIV infection, malnutrition, smoking, diabetes, alcohol abuse, and indoor air pollution. Preventive interventions may target these factors directly or via their underlying social determinants. The identification of risk groups also helps to target strategies for early detection of people in need of TB treatment. More research is needed on the suitability, feasibility and cost-effectiveness of these intervention options.