Comparative pathogenicity of Coxsackievirus A16 circulating and noncirculating strains in vitro and in a neonatal mouse model

An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain.

Changes in circulating endothelial progenitor cells predict responses of multiple myeloma patients to treatment with bortezomib and dexamethasone

Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM) patients. We investigated whether circulating endothelial progenitor cells (cEPCs) could be a biomarker for predicting patient response in the first cycle of chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs and stromal cell-derived factor-1α (SDF-1α) in 46 MM patients in the first cycle of treatment with bortezomib and dexamethasone, and investigated clinical relevance based on patient response after four 21-day cycles. The mononuclear cell fraction was analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study population was divided into 3 groups according to the response to chemotherapy: good responders (n=16), common responders (n=12), and non-responders (n=18). There were no significant differences among these groups at baseline day 1 (P>0.05). cEPC levels decreased slightly at day 21 (8.2±3.3 cEPCs/μL) vs day 1 (8.4±2.9 cEPCs/μL) in good responders (P>0.05). In contrast, cEPC levels increased significantly in the other two groups (P<0.05). SDF-1α changes were closely related to changes in cEPCs. These findings indicate that change in cEPCs at day 21 in the first cycle might be considered a noninvasive biomarker for predicting a later response, and extent of change could help decide whether to continue this costly chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for improved response and outcomes in MM patients.

Role of a GenoType MTBDRplus line probe assay in early detection of multidrug-resistant tuberculosis at a Brazilian reference center

Resistance to Mycobacterium tuberculosis is a reality worldwide, and its diagnosis continues to be difficult and time consuming. To face this challenge, the World Health Organization has recommended the use of rapid molecular tests. We evaluated the routine use (once a week) of a line probe assay (Genotype MTBDRplus) for early diagnosis of resistance and for assessment of the main related risk factors over 2 years. A total of 170 samples were tested: 15 (8.8%) were resistant, and multidrug resistance was detected in 10 (5.9%). The sensitivity profile took 3 weeks (2 weeks for culture and 1 week for rapid testing). Previous treatment for tuberculosis and the persistence of positive acid-fast smears after 4 months of supervised treatment were the major risk factors observed. The use of molecular tests enabled early diagnosis of drug-resistant bacilli and led to appropriate treatment of the disease. This information has the potential to interrupt the transmission chain of resistant M. tuberculosis.