Volume 04 · Issue 02 · 2024

在世界卫生组织（世卫组织）于2020年3月宣布冠状病毒疾病2019（新冠肺炎）大流行后，实施最有效的干预措施成为全球应对新冠肺炎大流行的首要公共卫生优先事项，特别是在疫苗可用之前。几项研究表明，非药物干预（NPI），如社交距离、戴口罩和学校关闭，可以大大控制呼吸道感染的传播，包括严重急性呼吸综合征、2009年的疫情H1N1和新冠肺炎疫情。^[1,2,3]然而，自新冠肺炎疫情以来，各种呼吸道感染变得更加普遍。自2021年以来，呼吸道合胞病毒（RSV）的发病率在包括美国、^[4]澳大利亚，^[5]英格兰，^[6]意大利，^[7]德国，^[8]还有瑞士。^[9]2022年12月，包括法国和英国在内的5个欧洲国家报告了A组链球菌感染的增加。^[10]自2023年10月中旬以来，中国监测系统观察到由以下原因引起的呼吸道感染呈上升趋势：肺炎支原体在中国北方的儿童中。^[11]此外，季节性流感的全球格局受到新冠肺炎疫情的显著影响，导致其流行模式发生显著变化（图1).

流感病毒在世界范围内导致呼吸道疾病，包括严重的下呼吸道疾病、住院和死亡。全球每年约有10亿例季节性流感病例，包括300万至500万例重症病例和29万至65万例呼吸道死亡。^[1]疫苗接种仍然是预防流感病毒在人类中传播引起的发病率和死亡率的最佳可用干预措施，特别是对于患有潜在健康状况（如哮喘、糖尿病和心血管疾病）的老年人。感染流感病毒可导致最大的发病率和死亡率影响。^[2]然而，传统的标准剂量灭活流感疫苗的有效性并不令人满意，在疫苗与循环病毒株抗原性不匹配的年份中，疫苗有效性范围为20%^[3]在疫苗抗原性良好匹配的年份中为40%至60%。^[4]每年的流感疫苗接种覆盖率很低，特别是在发展中国家。在中国，流感疫苗接种在整个人群中的年度覆盖率非常低，2014年至2021年期间的估计覆盖率在0.74%至2.94%之间变化。^[5]2022年，这一比例为2.47%。^[6]因此，需要具有改进的有效性的更好的流感疫苗和疫苗接种策略。

肺炎支原体是社区获得性肺炎的主要病原体，占社区获得性肺炎的10%至40%，并表现出不同的周期性流行模式，每3至7年复发一次。^[1,2,3,4]世界各国在疫情期间使用的针对冠状病毒疾病2019（新冠肺炎）的非药物干预措施（NPIs）显著降低了肺炎支原体.^[5]在新冠疫情限制措施解除后，肺炎支原体逐渐在全球范围内增长。^[6]为了更好地了解肺炎支原体2023年，我们探讨了肺炎支原体。

Human immunodeficiency virus type 1 (HIV-1) remains a persistent global health challenge. Therefore, a continuous exploration of novel therapeutic strategies is essential. A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic approaches.

In this study, we performed a flux balance analysis using a genome-scale metabolic model (GEM) integrated with an HIV-1 viral biomass objective function to identify potential targets for anti-HIV-1 interventions. We generated a GEM by integrating an HIV-1 production reaction into CD4+ T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion production. Differential analysis was used to predict biochemical reactions altered optimal for HIV-1 production. In addition, we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti-HIV-1 targets, which were subsequently validated by human phytohemagglutinin (PHA) blasts infected with HIV-1.

Differential analysis identified several altered biochemical reactions, including increased lysine uptake and oxidative phosphorylation (OXPHOS) activities in the virus optima compared with the host optima. In silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis, and OXPHOS could serve as potential anti-HIV-1 metabolic targets. In vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6% (385.4 ± 67.5 pg/mL in the metformin-treated group vs. 888.4 ± 32.3 pg/mL in the control group, P < 0.001).

Our integrated host-virus genome-scale metabolic study provides insights on potential targets (OXPHOS) for anti-HIV therapies.

Malaria remains a significant public health concern in Ghana, with varying risk levels across different geographical areas. Malaria affects millions of people each year and imposes a substantial burden on the health care system and population. Accurate risk estimation and mapping are crucial for effectively allocating resources and implementing targeted interventions to identify regions with disease hotspots. This study aimed to identify regions exhibiting elevated malaria risk so that public health interventions can be implemented, and to identify malaria risk predictors that can be controlled as part of public health interventions for malaria control.

The data on laboratory-confirmed malaria cases from 2015 to 2021 were obtained from the Ghana Health Service and Ghana Statistical Service. We studied the spatial and spatiotemporal patterns of the relative risk of malaria using Bayesian spatial and spatiotemporal models. The malaria risk for each region was mapped to visually identify regions with malaria hotspots. Clustering and heterogeneity of disease risks were established using correlated and uncorrelated structures via the conditional autoregressive and Gaussian models, respectively. Parameter estimates from the marginal posterior distribution were estimated within the Integrated Nested Laplace Approximation using the R software.

The spatial model indicated an increased risk of malaria in the North East, Bono East, Ahafo, Central, Upper West, Brong Ahafo, Ashanti, and Eastern regions. The spatiotemporal model results highlighted an elevated malaria risk in the North East, Upper West, Upper East, Savannah, Bono East, Central, Bono, and Ahafo regions. Both spatial and spatiotemporal models identified the North East, Upper West, Bono East, Central, and Ahafo Regions as hotspots for malaria risk. Substantial variations in risk were evident across regions (H = 104.9, P < 0.001). Although climatic and economic factors influenced malaria infection, statistical significance was not established.

Malaria risk was clustered and varied among regions in Ghana. There are many regions in Ghana that are hotspots for malaria risk, and climate and economic factors have no significant influence on malaria risk. This study could provide information on malaria transmission patterns in Ghana, and contribute to enhance the effectiveness of malaria control strategies.

Antimicrobial resistance is a global concern that has led to millions of deaths worldwide. Genetic changes occur naturally in pathogens such as viruses, bacteria, parasites, and fungi. To overcome these concerns, there is a need to develop a new generation of antimicrobials. In an effort to encourage innovation, both the United States (US) and the European Union have introduced exclusivity programs. The US offered 5 years of additional nonpatent exclusivity for Qualified Infectious Disease Products under the Generating Antibiotic Incentives Now Act. In parallel, the European Commission offers a patent extension of 12 months across Europe (EU) countries or the option to sell the vouchers to other pharmaceutical companies through transferable exclusivity extension vouchers. This review focuses on the most important innovative strategies of antibiotic development the drug approvals, their mode of action, spectra of activity, and targeting of microorganisms, in past 5 years were mentioned, and discusses how to overcome the challenges of drug approval under antibiotic exclusivity in the US and EU, which will benefit the companies to develop novel drugs in several nations.

The dynamics of COVID-19 and mucormycosis reveal a complex interplay of genetic factors that influence the susceptibility, severity, and immune responses. COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits an increased incidence of mucormycosis, particularly in individuals with comorbidities or corticosteroid therapy. Mucormycosis is a fungal infection that affects the sinuses, orbits, and lungs and demands timely intervention with antifungal medications and surgery because of its life-threatening nature. Research on the genetic underpinnings of this intersection has unveiled key insights into the pathogenicity of Mucorales. Breakthroughs in genetic tools have exposed virulence factors, such as the CotH protein family and high-affinity iron-uptake mechanisms. Genetic susceptibility is a pivotal element in identifying individuals at risk of developing COVID-19, facilitating early detection, and allowing for personalized treatment strategies. DPP9, MIF, and TYK2 are among the genes implicated in COVID-19 severity, emphasizing the intricate relationship between genetic makeup and viral response. The genetic landscape extends to viral entry mechanisms, thereby affecting infection efficiency. Specific polymorphisms in genes such as IFNAR2, OAS3, and TYK2 are associated with COVID-19 severity, indicating shared genetic bases between severe and hospitalized cases. Mucormycosis is genetically predisposed, particularly in immunocompromised individuals. The challenge lies in understanding the genetic factors influencing susceptibility and offering insights into pathogenesis and potential therapeutic avenues. Organ transplantation adds another layer, increasing susceptibility to infections such as COVID-19 and mucormycosis. The impact of immunosuppression on COVID-19 severity remains elusive, necessitating ongoing research on the immunological mechanisms. Despite the challenges posed by emerging SARS-CoV-2 variants, the intricate connection between genetic factors and the interplay of COVID-19 and mucormycosis presents an opportunity for personalized treatment, targeted interventions, and refined public health strategies.

Emphysematous gastritis (EG) is a rare form of gastritis characterized by gastric wall pneumatosis. It is associated with a high mortality rate. Our case report describes a patient with a history of atrial fibrillation treated with apixaban, prior stroke, and schizoaffective disorder who showed epigastric tenderness on examination. However, no peritonitis signs were recorded, and laboratory values revealed high lactate levels and the presence of adenovirus F40/41. Abdominal computed tomography scan showed extensive portal venous gas in the left hepatic lobe of the liver, as well as pneumatosis involving the entire stomach, indicating EG. The diagnosis was histologically confirmed and initially managed medically, which proved inefficacious, necessitating surgical intervention in the form of a laparotomy and esophagojejunostomy with Roux-en-Y reconstruction. This case report suggests a potential association between EG and adenovirus F40/41-induced gastroenteritis, thereby emphasizing the challenging nature of EG. It underscores the need for comprehensive research to enhance our understanding of its underlying causes and effective treatment strategies.

第四届艾滋病重大挑战研讨会于2023年12月28日在中国北京举行。王福生（国家传染病临床医学研究中心）和张林琦（清华大学医学院）作为大会主席组织了本次会议。大会上，几乎所有来自中国的获得性免疫缺陷综合征（AIDS）领域著名顶尖科学家和临床医生（图1）应邀介绍和讨论人类免疫缺陷病毒（HIV）治愈科学的最新进展，分享新技术、新疗法和新成果，并希望在艾滋病干预和艾滋病功能性治愈方面取得重大突破。

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