We investigated the epidemiology of extrapulmonary tuberculosis (TB) among patients admitted to Beijing Chest Hospital, Beijing, China, during January 2008–December 2017. Of 19,279 hospitalized TB patients, 33.4% (6,433) had extrapulmonary TB and 66.6% (12,846) had pulmonary TB. The most frequent forms of extrapulmonary TB observed were skeletal TB (41.1%) and pleural TB (26.0%). Younger, female patients from rural areas were more likely to have extrapulmonary TB. However, patients with diabetes mellitus were less likely to have extrapulmonary TB compared with patients without diabetes. A higher proportion of multidrug-resistant (MDR) TB was observed among patients with extrapulmonary TB than among patients with pulmonary TB. We observed a large increase in MDR TB, from 17.3% to 35.7%, for pleural TB cases. The increasing rate of drug resistance among extrapulmonary TB cases highlights the need for drug susceptibility testing and the formulation of more effective regimens for extrapulmonary TB treatment.

Clofazimine has been repurposed for the treatment of tuberculosis, especially for multidrug-resistant tuberculosis (MDR-TB). To test the susceptibility to clofazimine of Mycobacterium tuberculosis clinical isolates, MICs of clofazimine were determined using the microplate alamarBlue assay (MABA) method for 80 drugresistant isolates and 10 drug-susceptible isolates for comparison. For five clofazimineresistant strains isolated from previously treated pre-extensively drug-resistant TB (pre-XDR-TB) and XDR-TB patients without prior exposure to clofazimine or bedaquiline, clofazimine MICs were Ն1.2 g/ml. Four isolates with cross-resistance to bedaquiline had Rv0678 mutations. The other isolate with no resistance to bedaquiline had an Rv1979c mutation. This study adds to a recent study showing that 6.3% of MDR-TB patients without prior clofazimine or bedaquiline exposure harbored isolates with Rv0678 mutations, which raises concern that preexisting resistance to these drugs may be associated with prior TB treatment. Furthermore, we propose a tentative breakpoint of 1.2 g/ml for clofazimine resistance using the MABA method. Morewidespread surveillance and individualized testing for clofazimine and bedaquiline resistance, together with assessment of their clinical usage, especially among previously treated and MDR-TB patients, are warranted.

Members of Myxozoa, a parasitic metazoan taxon, have considerable detrimental effects on fish hosts and also have been associated with human food-borne illness. Little is known about their biology and metabolism. Analysis of the genome of Thelohanellus kitauei and comparative analysis with genomes of its two free-living cnidarian relatives revealed that T. kitauei has adapted to parasitism, as indicated by the streamlined metabolic repertoire and the tendency toward anabolism rather than catabolism. Thelohanellus kitauei mainly secretes proteases and protease inhibitors for nutrient digestion (parasite invasion), and depends on endocytosis (mainly low-density lipoprotein receptors-mediated type) and secondary carriers for nutrient absorption. Absence of both classic and complementary anaerobic pathways and gluconeogenesis, the lack of de novo synthesis and reduced activity in hydrolysis of fatty acids, amino acids, and nucleotides indicated that T. kitauei in this vertebrate host–parasite system has adapted to inhabit a physiological environment extremely rich in both oxygen and nutrients (especially glucose), which is consistent with its preferred parasitic site, that is, the host gut submucosa. Taking advantage of the genomic and transcriptomic information, 23 potential nutrition-related T. kitauei-specific chemotherapeutic targets were identified. This first genome sequence of a myxozoan will facilitate development of potential therapeutics for efficient control of myxozoan parasites and ultimately prevent myxozoan-induced fish-borne illnesses in humans.