In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

Background: Osimertinib (AZD9291) is a third‐generation EGFR‐tyrosine kinase inhibitor (TKI) that selectively inhibits the activating EGFR mutation and T790M mutation, and is currently used globally to treat EGFR‐mutant non‐small cell lung cancer (NSCLC). However, acquired resistance to osimertinib is inevitable.Methods: We established osimertinib‐resistant cells (PC9/T790M/AZDR and H1975/AZDR) derived from EGFR‐mutant NSCLC cells harboring T790M mutation, and investigated the mechanism of acquired resistance to osimertinib by whole‐exome sequencing and multiple phospho‐receptor tyrosine kinase (RTK) array. A tumor specimen from an EGFR‐mutant NSCLC patient with acquired resistance to osimertinib was also subjected to immunohistochemical analysis.Results: Whole‐exome sequencing analysis demonstrated that genetic alterations, such as acquisition of EGFR C797S, loss of T790M mutation, MET amplification, or mutated KRAS, MEK, BRAF, PIK3CA, were not detected. Analysis of phospho‐RTK array revealed that insulin‐like growth factor‐1 receptor (IGF1R) was activated in PC9/T790M/AZDR and H1975/AZDR cells. Knockdown of IGF1R by siRNA as well as inhibition of IGF1R activation by linstinib (IGF1R inhibitor) significantly restored the sensitivity to osimertinib. Immunohistochemical analysis revealed that the expression level of phosphorylated IGF1R was higher in the tumor specimen from the EGFR‐mutant NSCLC patient with acquired resistance to osimertinib than in the specimen collected prior to the treatment.Conclusions: IGF1R activation could occur following treatment with osimertinib in EGFR‐mutant NSCLC with T790M mutation, and might be one of the mechanisms underlying osimertinib resistance. Combined treatment of osimertinib and IGF1R inhibitor might be effective in overcoming the acquired resistance to osimertinib induced by IGF1R activation.Key points: Significant findings of the study: Using osimertinib‐resistant cells, we found that IGF1R activation induced by osimertinib treatment in EGFR‐mutant NSCLC with T790M mutation is involved in resistance. Increased phosphorylation of IGF1R was observed in the tumor specimen from an EGFR‐mutant NSCLC patient with acquired osimertinib resistance.What this study adds: IGF1R activation might be one of the mechanisms of osimertinib resistance. A combination therapy with osimertinib and an IGF1R inhibitor might be an optimal approach for overcoming the acquired resistance to osimertinib induced by IGF1R activation.

Several epidemiology studies suggest that host genetic factors play important roles in susceptibility, protection and progression of tuberculosis infection. Here we have reviewed the implications of some genetic polymorphisms in pathways related to tuberculosis susceptibility, severity and development. Large case-control studies examining single-nucleotide polymorphisms (SNPs) in genes have been performed in tuberculosis patients in some countries. Polymorphisms in natural resistance-associated macrophage protein 1 (NRAMP1), toll-like receptor 2 (TLR2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1 receptor antagonist (IL-1RA), IL-10, vitamin D receptor (VDR), dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), monocyte chemoattractant protein-1 (MCP-1), nucleotide oligomerization binding domain 2 (NOD2), interferon-gamma (IFN-γ), inducible nitric oxide synthase (iNOS), mannose-binding lectin (MBL) and surfactant proteins A (SP-A) have been reviewed. These genes have been variably associated with tuberculosis infection and there is strong evidence indicating that host genetic factors play critical roles in tuberculosis susceptibility, severity and development.

Obtaining a booster dose of coronavirus disease 2019 (COVID-19) vaccine is required to maintain the protective level of neutralizing antibodies and therefore herd immunity in the community, and the success of booster dose programs depends on public acceptance. The aim of this study was to determine the acceptance of a booster dose of COVID-19 vaccine and its drivers and barriers in Indonesia. A cross-sectional survey was conducted in the provinces of Indonesia between 1 and 15 August 2022. Individuals who completed the primary series of the COVID-19 vaccine were asked about their acceptance of a booster dose. Those who refused the booster dose were questioned about their reasons. A logistic regression was used to determine the determinants associated with rejection of a booster dose of COVID-19 vaccine. A total of 2935 respondents were included in the final analysis. With no information on the efficacy and safety of the COVID-19 vaccine, 95% of respondents agreed to receive a booster dose if it were provided for free by the government. This acceptance was reduced to only 50.3% if the vaccine had a 75% efficacy with a 20% chance of side effects. The adjusted logistic regression analysis indicated that there were eight factors associated with the rejection of the booster dose: age, marital status, religion, occupation, type of the first two vaccines received, knowledge regarding the importance of the booster dose, belief that natural immunity is sufficient to prevent COVID-19 and disbelief in the effectiveness of the booster dose. In conclusion, the hesitancy toward booster doses in Indonesia is influenced by some intrinsic factors such as lack of knowledge on the benefits of the booster dose, worries regarding the unexpected side effects and concerns about the halal status of the provided vaccines and extrinsic determinants such as the effectiveness and safety of the vaccine. These findings suggest the need for more campaigns and promotions regarding the booster dose benefits to increase its acceptance.