Evaluation of Xpert MTB/RIF for the Diagnosis of Extrapulmonary Tuberculosis in China

We evaluate the performance of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis （EPTB） in China. The performance of Xpert was evaluated compared to the composite reference standard （CRS）, drug susceptibility testing （DST）, and imaging examination. The overall sensitivity and specificity of Xpert were 64.1% （195/304） and 100% （24/24）, respectively, using CRS as the gold standard. The sensitivity was significantly higher than that of culture for pus （P〈0.05）. The proportion of EPTB-positive cases diagnosed by imaging was two times more than that diagnosed using Xpert; however, 6 out of 19 cases may have been overdiagnosed by imaging.

Evaluation of Lo＂wenstein-Jensen Medium Culture,MGIT 960 Culture and Different Specimen Types inDiagnosis of Bone and Joint Tuberculosis

Objective： The aim of this study was to evaluate L-J （Lo＂wenstein-Jensen） medium culture, MGIT 960 culture anddifferent specimen types in diagnosis of BJTB （bone and joint tuberculosis）. Methods：： Specimens of pus, caseous necrosis,tuberculous granuloma and sequestrum were collected from 52 BJTB patients. All specimens were cultured using both MGIT 960system and L-J medium; and all pus were amplified using real-time PCR to detect the presence of M. tuberculosis DNA. KeyFindings： A total of 191 specimens were collected. Granuloma had better chance to produce positive outcomes by L-J mediumculture, while for sequestrum MGIT 960 culture had higher yield, but there was no significant difference in the recovery rates amongdifferent types of specimen either by L-J culture （Z2 = 0.638, P = 0.888） or by MGIT960 culture （Z2 = 1.399, P = 0.706）. MGIT960culture had significantly higher recovery rate than L-J culture, With a combined culture and PCR-based test, the recovery rate of pusspecimen was significantly higher than that of either method alone （P 〈 0.05）. Conclusion： MGIT 960 culture is superior to L-Jculture in BJTB diagnosis; pus, sequestrum, granuloma and caseous necrosis are usable specimen for mycobacterial culture;combination of culture and molecular techniques can provide a better diagnostic significance.

The rLrp of Mycobacterium tuberculosis inhibits proinflammatory cytokine production and downregulates APC function in mouse macrophages via a TLR2-mediated PI3K/Akt pathway activation-dependent mechanism

We demonstrate that Mycobacterium tuberculosis recombinant leucine-responsive regulatory protein （rLrp） inhibits lipopolysaccharide （LPS）-induced tumor necrosis factor alpha （TNF-a）, interleukin-6, and interleukin-12 production and blocks the nuclear translocation of subunits of the nuclear-receptor transcription factor NF-KB （Nuclear factor-kappa B）. Moreover, rLrp attenuated LPS-induced DNA binding and NF-κB transcriptional activity, which was accompanied by the degradation of inhibitory IκBα and a consequent decrease in the nuclear translocation of the NF-κB p65 subunit. RLrp interfered with the LPS-induced clustering of TNF receptor-associated factor 6 and with interleukin-1 receptor-associated kinase 1 binding to TAKI. Furthermore, rLrp did not attenuate proinflammatory cytokines or the expression of CD86 and major histocompatibility complex class-II induced by interferon-gamma in the macrophages of Toll-like receptor 2 deletion （TLR2-/-） mice and in protein kinase b （Akt）-depleted mouse cells, indicating that the inhibitory effects of rLrp were dependent on TLR2-mediated activation of the phosphatidylinositol 3-OH kinase （PI3K）/ Akt pathway. RLrp could also activate the PI3K/Akt pathway by stimulating the rapid phosphorylation of PI3K, Akt, and glycogen synthase kinase 3 beta in macrophages. In addition, 19 amino acid residues in the N-terminus of rLrp were determined to be important and required for the inhibitory effects mediated by TLR2. The inhibitory function of these 19 amino acids of rLrp raises the possibility that mimetic inhibitory peptides could be used to restrict innate immune responses in situations in which prolonged TLR signaling has deleterious effects. Our study offers new insight into the inhibitory mechanisms by which the TLR2-mediated PI3K/Akt pathway ensures the transient expression of potent inflammatory mediators.

Treatment of coronavirus disease 2019 in Shandong,China:a cost and affordability analysis

Background:Coronavirus disease 2019(COVID-19)is now a global public threat.Given the pandemic of COVID-19,the economic impact of COVID-19 is essential to add value to the policy-making process.We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China,and also assess the factors affecting their costs.Methods:This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020.The total direct medical expenditures were analyzed by cost factors.We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income.Differences between groups were tested by student t test and Mann-Whitney test when appropriate.A multiple logistic regression model was built to determine the risk factors associated with high cost.Results:A total of 70 COVID-19 patients were included in the analysis.The overall mean cost was USD 6827 per treated episode.The highest mean cost was observed in drug acquisition,accounting for 45.1%of the overall cost.Total mean cost was significantly higher in patients with pre-existing diseases compared to those without preexisting diseases.Pre-existing diseases and the advanced disease severity were strongly associated with higher cost.Around USD 0.49 billion were expected for clinical manage of COVID-19 in China.Among rural households,the proportions of health insurance coverage should be increased to 70%for severe cases,and 80%for critically ill cases to avoid catastrophic health expenditure.Conclusions:Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance.The cost for drug acquisition is the major contributor to the medical cost,whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19.Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.