2021年 · 第03卷第06期

The treatment of K. pneumoniae infections has become more difficult due to the emergence of multidrug-resistant strains. This study aimed to evaluate antimicrobial resistance patterns and detect different types of beta-lactamase genes among MDR and non-MDR Klebsiella pneumoniae in various clinical samples. A total of 150 Klebsiella pneumoniae were identified from different clinical samples by conventional microbiological procedures. Antibiotic sensitivity was detected by the Kirby-Bauer disc diffusion method. Extended-spectrum beta-lactamase, Metallo-β-lactamase, and carbapenemase were phenotypically detected by double-disk synergy test, combined disk assay, and modified Hodge test. PCR also detected different β lactamase genes and virulence genes. The majority of Klebsiella pneumoniae were multi-drug resistant (82%). The bacteria were found resistant to most β-lactam antibiotics, aminoglycosides, ciprofloxacin, cotrimoxazole, carbapenem, piperacillin, and tazobactam. However, only about 0.7% colistin resistance was observed. A double-disk synergy test was performed among the isolates for phenotypic detection of ESBL producing Klebsiella pneumoniae. Only 16.6% of isolates were found to be ESBL producers. Among β-lactamase genes, NDM (23.34%), OXA-48(8%), and KPC (7.3%) were detected. Other prevalent β lactamase genes VIM and IMP were not detected. In summary, the prevalence of MDR Klebsiella pneumoniae is high in Bangladesh, which may complicate the treatment of hospitalized patients.

By re-analzying public metagenomic data from 101 patients infected with influenza A virus during the 2007-2012 H1N1 flu seasons in France, we identified 22 samples with SARS-CoV sequences. In three of them, the SARS genome sequences could be fully assembled out of each. These sequences are highly similar (99.99% and 99.70%) to the artificially constructed recombinant SARS-CoV (SARSr-CoV) strains generated by the J. Craig Venter Institute in the USA. Moreover, samples from different flu seasons have different SARS-CoV strains, and the divergence between these strains cannot be explained by natural evolution. Our study also shows that retrospective studies using public metagenomic data from past major epidemic outbreaks serve as a genomic strategy for the research of the origins or spread of infectious diseases.

Since the outbreak at the end of 2019, SARS-CoV-2 has been spreading around the world for more than one year. Scientists have been intensely conducting research on this newly emerged coronavirus and the disease caused by it. Angiotensin-converting enzyme 2 (ACE2), as a receptor mediating the cellular entry of SARS-CoV-2, has become a hot spot for researchers. Here, we summarized the recent progresses on the function, expression and distribution characteristics of ACE2 in human body and among populations. We further discussed the interaction mechanism of ACE2 and SARS-CoV-2 S protein, focusing on key residues that effect interaction and binding ability of SARS-CoV-2 variants. This will facilitate researchers to better understand SARS-CoV-2 infection and transmission route, adaptation mechanism, and designing treatment strategies.

To assess the tuberculosis (TB) epidemic and incidence trends in areas and countries along the Belt and Road Initiative, we analyzed the prevalence, diagnosis, and treatment of tuberculosis through consulting the data of the World Health Organization’s Global Tuberculosis Report. We estimated the tuberculosis incidence trends in these countries using joinpoint regression. Among the 65 countries along the route, in addition to Palestine with no relevant data, the incidence rate was 181.5 per 100,000, and the mortality rate was 23.1 per 100,000 in 2018. Both the incidence rates in 26 countries and the mortalities in 32 countries were higher than in China. Among the regions, the incidence and mortality of tuberculosis were the highest in South Asia, East Asia, and The Association of Southeast Asia Nations (ASEAN) countries, while the tuberculosis detection rate and positive bacteriological rate were the lowest in East Asia and ASEAN countries. Average yearly incidence decreased from 235.7 per 100,000 in 2004 to 181.5 per 100,000 in 2018 (average annual percentage change 1.9%) in these countries. Although TB incidence of most countries along the Belt and Road Initiative was declining, the rate of decrease was not yet fast enough. Therefore, it is essential to establish the exchange and cooperation mechanism of TB prevention and control experience among different countries, strengthen information com-munication and sharing, and explore a cross-border notification system. In addition, TB detection of interna-tional travelers should be carried out and improved.

Early and accurate diagnosis of human prion diseases is a long-standing difficulty. Currently, the definitive diagnosis of human prion diseases relies on pathognomonic histological features or PrPSc detection of patients' brain tissue biopsy or autopsy samples, which is not feasible in most cases. Therefore, clinical diagnosis mainly relies on the combinations of the patient’s clinical symptoms. MRI and EEG are used to check for brain damage and detect surrogate markers such as the 14-3-3 protein in Cerebrospinal fluid (CSF), but this is often challenging. In recent years, the development of in vitro cell-free conversion techniques, such as technologies protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC), have extensively promoted the diagnosis of human prion diseases. PMCA has high diagnostic accuracy in the blood, CSF, and urine samples of variant creutzfeldt-jakob disease (vCJD) patients. Again, RT-QuIC has high diagnostic accuracy for cerebrospinal fluid, olfactory mucosa, and skin samples of sporadic Creutzfeldt Jakob Disease (sCJD) patients. Applying these two technologies is of great significance to the early clinical diagnosis of human prion diseases and the reduction of blood-borne and iatrogenic transmission of prion.

Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus (DENV). DENV causes a febrile illness, severe forms including hemorrhagic fevers and shock with fatalities in humans. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 strains from Guangdong, China, have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo. A total of 22 patients tested to be DENV-2 positive and were enrolled in this study, 22 complete genomes were obtained by virus isolation and high-throughput sequencing. Phylogenetic and single amino polymorphism (SAP) analysis indicated that two major subgenotypes (A and C) of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018. The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains, including endemic genotype and imported genotype. It alerted the risk of cross-border transmission of DENV. A significant difference in replication rate was observed in C6/36 between different DENV-2 strains, although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles. DENV-2 subgenotypes (A and C) replicated efficiently in IFNAR^-/- C57BL/6 mice, and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group. DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo, indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.

Severe pneumonia in patients infected with the 2009 pandemic H1N1 (pH1N1) virus was partially attributed to excessive immune response. Anti-virus treatment for these patients was insufficient. Here we reported the therapy effect of sirolimus, an immunosuppressor, combined with oseltamivir and corticosteroid for a puerpera with severe pneumonia caused by pH1N1 virus. This patient has infected with the pH1N1 virus in late pregnancy, and antiviral therapy was not implemented timely. She developed severe pneumonia and ARDS rapidly and need receive a cesarean section on the 39th week after pregnancy. After giving birth to a healthy baby, she received a combination of oseltamivir, sirolimus and corticosteroid, and improved in the following days. Moreover, the cytokines in serum and viral loads in BALF decreased significantly. She recovered without infectious symptoms and was discharged. Sirolimus combined with oseltamivir and corticosteroid is likely responsible for lowering the viral loads, reducing the patient's cytokine level, and further improving her clinical outcomes. It provides evidence that adjuvant treatment was beneficial to patients with severe pneumonia induced by the pH1N1 virus.